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.3 Clearly, BT has the capability of R L Tomsak LETTERS causing central nervous system side effects. Departments of Neurology and Ophthalmology, Oral clonidine, another α-2 adrenergic ago- Division of Clinical Neuro-ophthalmology, nist, is known to cause visual hallucinations. University Hospitals of Cleveland, LKSD 3200, Charles Bonnet syndrome Brown and coworkers6 described the case of a 1100 Euclid Avenue, Cleveland, OH 44106, USA precipitated by brimonidine 31 year old woman treated with clonidine for C R Zaret tartrate eye drops poorly controlled hypertension who devel- Departments of Ophthalmology and Neurology, oped visions of “hands reaching for her from The Feinberg School of Medicine, Northwestern Brimonidine tartrate (BT) (Alphagan) is an a closet or an old woman following her” in the University, Chicago, IL, USA α-2 adrenergic agonist marketed for treat- presence of an otherwise clear sensorium. ment of primary open angle glaucoma Also, clonidine use has caused delusional psy- D Weidenthal (POAG) which may have neuroprotective choses and auditory hallucinations in other Department of Ophthalmology, Case Western 1 effects. One report of acute delusional psy- patients.78 Reserve University School of Medicine, Cleveland, OH, USA chosis with auditory hallucinations in a 68 All of our patients were at risk for the CBS year old man treated for POAG has been based on age and but none 2 Correspondence to: Dr Robert L Tomsak, published, and use of BT eye drops in an had had visual hallucinations before using BT. Departments of Neurology and Ophthalmology, infant resulted in coma and other serious sys- Division of Clinical Neuro-ophthalmology, 3 The onset of CBS ranged from 5 days to 2.5 temic abnormalities. Here we report four eld- months from starting BT. The visual halluci- University Hospitals of Cleveland, LKSD 3200, erly patients with bilateral visual loss who nations ceased in three of our patients within 1100 Euclid Ave., Cleveland, OH 44106, USA; [email protected] developed formed visual hallucinations days of discontinuing BT (cases 1 and 3) or (Charles Bonnet syndrome; CBS) shortly after decreasing the dose (case 4), consistent with Accepted for publication 9 November 2002 beginning the use of BT eye drops. The hallu- the washout period of the drug. In case 2, the cinations ceased after discontinuation of BT hallucinations lasted on and off for about 4 References drops in three cases, and after decreasing the months. Therefore the persistence of the hal- 1 Gao H, Qioa X, Cantor LB, et al. dose in one case, within a time frame of days lucinations cannot be explained directly by Up-regulation of -derived neurotrophic to 4 months. persistent drug toxicity in this person. How- factor expression by brimonidine in rat retinal ever, it is still possible that BT triggered the ganglion cells. Arch Ophthalmol Case reports 2002;120:797–803. start of CBS in this individual. The natural Table 1 summarises visual function and the 2 Kim DD. A case of suspected history of duration of CBS is 47.4 months on characteristics of the visual hallucinations in Alphagan-induced psychosis. Arch average, with a range of 1–240 months.4 It all four patients. Ophthalmol 2000;118:1132–3. should be noted that patient 2 also was taking 3 Berlin RJ, Lee UT, Samples JR, et al. Comment a wide variety of drugs at the time BT was Ophthalmic drops causing coma in an infant. prescribed but their role, if any, in causing the J Pediatr 2001;138:441–3. The Charles Bonnet syndrome is characterised visual hallucinations to persist is uncertain. 4 Teunisse RJ, Zitman FG, Raes DCM. Clinical by persistent or repetitive formed visual evaluation of 14 patients with the Charles For example, one study found no statistical hallucinations in elderly individuals in the Bonnet syndrome (isolated visual setting of significant bilateral prechiasmal difference in the number of drugs taken by hallucinations). Comp Psychiatry visual impairment.4 The visual hallucinations patients seen in a geriatric psychiatry clinic 1994;35:70–5. who suffered from visual hallucinations when 5 Brimonidine (Management/Treatment in CBS are not routinely accompanied by http://bjo.bmj.com/ compared with a control group of elderly Protocol). In: Toll LL, Hurlbut, eds. Poisindex other psychiatric symptoms and the affected System. Vol 113. Greenwood Village, CO: individuals retain full or partial insight into patients without hallucinations (4.4 (SD 3.1) drugs in the group with hallucinations).9 Micromedex, 2002. the unreality of the visions. Brown MJ In summary, elderly people with bilateral 6 , Salmon D, Rendell M. Clonidine Brimonidine tartrate is a lipid soluble α-2 hallucinations. Ann Intern Med adrenergic agonist that has a systemic half life visual impairment should be warned of the 1980;93:456–7. of about 3 hours. It is excreted mainly by the possibility of visual hallucinations resulting 7 Lavin P, Alexander CP. Dementia associated kidneys with 87% of an oral dose eliminated from BT use. with clonidine therapy. BMJ 1975;1:628. after 120 hours.5 Auditory hallucinations, 8 Enoch MD, Hammad GEM. Acute depression, confusion, and anxiety have been Acknowledgement hallucinosis due to clonidine. Curr Med Res on September 28, 2021 by guest. Protected copyright. 2 Opin 1977;4:670–1. reported with BT use in an elderly adult and This work was supported in part by a gift from Lav- 9 Holroyd S. Visual hallucinations in a geriatric coma, hypotension, bradycardia, hypotonia, erne Kolbe Burke. psychiatry clinic: prevalence and associated and hypothermia was caused by BT eye drops Conflict of interest: None of the authors has a conflict diagnoses. J Geriatr Psychiatry Neurol given to an infant for treatment of of interest involving any aspect of this publication. 1996;9:171–5.

Table 1 Clinical characteristics

Age Sex VA Visual fields Visual hallucinations

79 F RE 20/20 Humphrey 24-2; constriction to 15 degrees; MD −16.68 dB “like dreaming while awake . . .water dripping from the ceiling” LE 20/25 Humphrey 24-2; complete loss of inferior nasal field; MD −12.61 dB

82 F RE 20/80 Humphrey 81-3 zone; 51/81 points not seen “A changing visual panorama . . .halls green with diamond-like LE FC Confrontation; FC ability in all but inferior nasal field pattern . . .blue flowers covering the bathroom . . .small red and grey tiles on the carpet . . .the walls looked like they were made of brick”

78 M RE 20/25 Humphrey 81-3 zone; 55/81 points not seen “I saw images of my bedroom wallpaper all over my house...” LE 5/200 Humphrey 81-3 zone; 50/81 points not seen

89 F RE 20/40 Humphrey 24-2; MD −3.14 Peopleintheroomthatwerenotthere...people or shadows LE 20/40 Humphrey 24-2; MD −11.66 standing near the elevator Dense inferior field defect

VA = visual acuity; MD = mean deviation; FC = finger counting.

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Trends in squint surgical activity new patient seen with a squint and another as “one and a half syndrome,” is most Br J Ophthalmol: first published as 10.1136/bjo.87.7.918-a on 1 July 2003. Downloaded from seen with a non-squint problem. While the commonly caused by demyelination, vascular It has recently been reported that there has proportion of children who required surgery disease or tumours.12 Ophthalmological been a trend in the United Kingdom towards had remained constant, there had been, simi- symptoms include , or 1 fewer children requiring surgery. lar to a recent report,1 a reduction in the blurred vision and are often remarkably chal- Unless there has been a change in the number of squint operations being per- lenging to manage.3 Since the introduction of incidence of childhood strabismus, it may formed, with a corresponding increase in the botulinum toxin A (BTA)4 for ocular motility reflect a change in the clinical practices of proportion of non-squint operations. We agree disorders and nystagmus5 there have been a ophthalmologists, optometrists, and orthop- that there were likely to have been a variety of number of reports that establish the use of tists. One such practice is the correction of other factors contributing to the reduction in BTA as a treatment option in the management associated refractive errors. The correction of a strabismus surgery. However, this trend may of complex ocular motility disorders. hypermetropic is an important reflect in part, a change in practice whereby We report the use of BTA in a patient with 1–4 aspect in the management of . children with strabismus who had a hyperme- one and a half syndrome. Although the full hypermetropic correction is tropic refractive error were, during the latter usually prescribed for children with an period, prescribed their full hypermetropic Case report esotropia, it is unclear whether this is, or has correction. A 52 year old white male patient was admitted been, uniform in practice. Indeed, certain to our institution with dysarthria and right texts suggest a reduction in the hyperme- J Shankar, S Kaye arm weakness of sudden onset. Three years tropic correction following a cycloplegic re- St Paul’s Eye Unit, 8Z Link, Royal Liverpool before he had suffered a post-coital subarach- fraction, to take into account so called accom- University Hospital, Prescot Street, noid haemorrhage from a right middle cer- modative tonus.4 Because of the effect of an Liverpool L7 8XP, UK ebral artery aneurysm. He had had his aneu- undercorrection of a hypermetropic refractive rysm clipped and had managed an almost Correspondence to: Stephen Kaye, St Paul’s Eye complete recovery. He was overweight and error on the angle of esotropia, we were inter- Unit, 8Z Link, Royal Liverpool University Hospital, ested to determine whether a change in spec- Prescot Street, Liverpool L7 8XP, UK; hypertensive. tacle prescribing practice had had any effect [email protected] When he was admitted it was noted that he on the number of patients undergoing squint had right facial weakness and his right eye surgery. Accepted for publication 13 November 2002 was abducted. Cranial imaging showed con- siderable volume loss and gliosis in the right Methods References frontoparietal region and a possible small in- Data were collected from the computerised 1 Carney CV, Lysons DA, Tapley JV. Is the farct in the right side of . A few days after hospital attendance statistics and operations incidence of constant esotropia in childhood the incident and when the patient regained 9 at the Royal Liverpool Children’s NHS Trust reducing? Eye 1995; :40–1. consciousness he complained of oscillopsia 2 Abrams D. Binocular muscle Hospital, which were available from the anomalies—heterotropia. Duke-Elder’s from his right eye and an ophthalmological financial year 1988–9 onwards. The annual practice of refraction. 9th ed. London: opinion was requested. number of ophthalmic referrals and opera- Churchill Livingstone, 1978:90. Examination of this patient was hampered tions, were collected within two time periods: 3 Elkington A, Frank H. Practical clinical by his poor mobility and severe dysarthria. He a 4 year period from 1988–9 to 1991–2 (period refraction. Clinical optics. 2nd ed. Oxford: was found to have a complete left gaze palsy 1)anda7yearperiodfrom 1994–5 to 2000–1 Blackwell Science, 1991:181. and a left INO. He was divergent in the (period 2). Before 1992, it had been the prac- 4 Bennett AC, Rabbets RB. Clinical visual primary position with an angle of approxi- tice to prescribe spectacles with a 0.5–1 optics. 2nd ed. Oxford: mately 45 prism dioptres (Krimsky). Vertical Butterworth-Heinemann, 1984:133. dioptre reduction in the spherical component eye movements were preserved, although he of the cycloplegic refractive error. From the was reluctant to elevate or depress his eyes period 1994 onwards, it was the practice of the Botulinum toxin treatment of and the examination of convergence was consultant for the full cycloplegic hyperme- “one and a half syndrome” inconclusive (Fig 1). His main symptom was tropic error to be prescribed. Data were not oscillopsia due to the abducting of collected between 1992 and 1994 to allow for Complex forms of nystagmus and conjugate his non-paretic right eye, which was only http://bjo.bmj.com/ a possible washout period for those patients eye movement deficits are generated if the relieved with occlusion of the eye with a who had previously been prescribed an pontine paramedian structures are damaged. patch. undercorrected hypermetropic correction and These can cause troublesome and occasionally A clinical diagnosis of one and a half were undergoing surgery between 1992 and disabling symptoms. The combination of one syndrome secondary to a cerebrovascular 1994. The total number of eye and squint sided horizontal gaze palsy and ipsilateral event was made. His concurrent is a operations performed per 100 patient refer- internuclear ophthalmoplegia (INO), known well described, even if uncommon feature of rals, and the ratio between the squint and

non-squint operations performed were calcu- on September 28, 2021 by guest. Protected copyright. lated. The difference between the two periods was compared using the Fisher’s exact test and confidence intervals calculated by the Miettinen approximation method. Results During periods 1 and 2, 4514 and 10 314 new patients were seen, of whom 23.9% and 23.6% underwent some form of ophthalmic surgery (p >0.5). There was a significant difference between the mean number of squint opera- tions per 100 patients in period 1 compared to period 2 (14.8% and 9.3%, p <0.0001, pro- portion difference 0.060, 95% CI 0.047 to 0.073). There was also a significant difference in the mean number of squint operations per 100 total operations performed in period 1 compared to period 2 (61.9% and 38.2%, p <0.0001, proportion difference 0.243, 95% CI 0.203 to 0.283). Comment Although it was not possible to examine the population profiles in the time periods stud- ied, there had been no known change in the population profile or referring practices. The hospital data retrieval system, unfortunately, Figure 1 Still photographs of eye movements before botulinum toxin. Permission for did not permit us to differentiate between a photograph given by patient.

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3 De Seze J, Lucas C, Leclerc X, et al. Br J Ophthalmol: first published as 10.1136/bjo.87.7.918-a on 1 July 2003. Downloaded from One-and-a-half syndrome in pontine infarcts: MRI correlates. Neuroradiology 1999;41:666–9. 4 Scott AB, Rosenbaum A, Collins CC. Pharmacologic weakening of . Invest Ophthalmol 1973;12:924–7. 5 Helveston EM, Pogrebniak AE. Treatment of acquired nystagmus with botulinum A toxin. Am J Ophthalmol 1988;106:584–6. 6 Kosmin AS, Marsh IB, Batterbury M. The use of botulinum toxin injections in the management of acquired nystagmus and oscillopsia. Clinical Rehabilitation 1996;10:205–9. 7 Tomsak RL, Remler BF, Averbuch-Heller L, et al. Unsatisfactory treatment of acquired nystagmus with retrobulbar injection of botulinum toxin. Am J Ophthalmol 1995;119:489–96. 8 Ruben ST, Lee JP, O’Neil D, et al. The use of botulinum toxin for treatment of acquired nystagmus and oscillopsia. Ophthalmology 1994;101:783–7.

Retinal and subdural Figure 2 Still photographs of eye movements 3 weeks after injection of botulinum toxin. haemorrhages: Aoki revisited Permission for photograph given by patient. In the United States and much of the English speaking world, the combination of retinal this syndrome and is explained by a tendency with BTA may abolish oscillopsia from nystag- and subdural haemorrhages in a very young of the contralateral eye to drift in the opposite mus but can cause oscillopsia during head child is highly suggestive of non-accidental 2 7 injury and felt to be incompatible with a his- direction due to the horizontal gaze palsy. movements. Our patient was so severely 1 Thus, one and a half syndrome has also been immobilised that this was not an issue, both tory of a minor fall. Thus, when Aoki et al called paralytic pontine exotropia. because of limited head movement and the published 26 cases of infants, age 3–14 Botulinum toxin was injected into the right fact that the vestibulo-ocular reflex is less months, with this combination following lateral rectus muscle under EMG control. essential in bed bound patients. There was a minimal falls, even though they stated in their Three weeks after the injection the patient’s definite subjective improvement in the quality article “in this series, none of the patients had symptoms had improved. In the primary posi- of life with the abolishment of his abducting a significant medical history or were subjects of child abuse before the trauma,” there was tion he showed only a very small amount of nystagmus. We have not been able to explain immediate concern2 that these may have been divergence. He had disposed of the patch as he the absence of diplopia after treatment, in undiagnosed cases of shaken baby syndrome had no oscillopsia. There was an abduction spite of a small residual divergence. (SBS). Aoki responded to this by saying “we deficit in the right eye, presumably as a result There has been a previous report of a do not believe the injuries were caused by of the BTA injection with elimination of the patient with one and a half syndrome treated battering or shaking” although noting their abducting nystagmus (Fig 2). with BTA8 but on that occasion the toxin was “series might include some injuries caused by Three months after BTA injection he re- administered into the retrobulbar space of the abuse.” In 1987, Ikeda et al3 added cases to the mained symptom free. He was still very eye ipsilateral to the INO. To our knowledge Japanese experience noting these were “usu- http://bjo.bmj.com/ slightly divergent in the primary position. His this is the first report of one and a half ally caused by a simple domestic head injury” left gaze palsy showed some mild improve- syndrome treated with a BTA injection in a ment without abducting nystagmus of the and indicating they were aware of the selected extraocular muscle. battered child syndrome. right eye. He did not report diplopia or In conclusion, injection of botulinum toxin oscillopsia. A comparison of the age distributions of the to selected extraocular muscles can provide a Aoki and Ikeda series shows them to be very useful alternative to occlusion, drug, or surgi- Comment similar (a simple t test not being able to rule cal therapies for patients with complex ataxic Eye symptoms following damage to pontine they are different with even a 20% probabil- nystagmus resulting from pontine lesions. ity). However, if either Japanese series or a structures have been shown to fluctuate with Patients suffering from oscillopsia due to on September 28, 2021 by guest. Protected copyright. time and often spontaneously resolve.2 How- combination of the two are compared to ataxic disconjugate nystagmus may benefit 4 ever, persistent symptoms can also occur. Kivlin’s SBS series in the United States, it is from this approach as most other treatments apparent these are not the same (the probabil- Intractable diplopia or oscillopsia of even a are unsuitable for such cases. There does not few months’ duration can prove functionally ity by a simple t test shows there to be seem to be any particular benefit in waiting between less than one chance in 400 and a disabling to the patients especially when bed for stabilisation of symptoms and signs. 6 chance in a million that these age distribu- bound. The transient nature of the BTA Selected toxin injection may improve the therapeutic effect makes it the most suitable tions are the same) (Tables 1 and 2). quality of life during the rehabilitation period. 56 management for these complex ocular motil- Recent articles have again brought into ity problems. A Kipioti, R H Taylor question the assumption that a history of a minimal fall is incompatible with the finding In our patient, although his one and a half York District Hospital,Wigginton Road, York syndrome was associated with exotropia, the YO3 7HE, UK of subdural haematoma and retinal haemor- main disturbance was caused by his acquired rhage in an infant. However, even if some of abducting nystagmus. It could be argued that Correspondence to: Miss Tina Kipioti, Eye the Japanese cases are from abuse, some of the duration of symptoms between presenta- Department, Clarendon Wing, Leeds General the American cases may be from minimal tion and administration of the toxin was not Infirmary, Leeds LS2 9NS, UK; falls. The United States assumption would sufficient to ensure that the condition would [email protected] require all the Japanese cases to be misdiag- not have resolved spontaneously. However, noses and all 26–40 independent stories in Accepted for publication 16 November 2002 the timing of symptom resolution despite the Japan (which are similar to many of the persistence of INO features suggest that the United States stories) to be similar prevarica- improvement was more probably due to the References tions. Instead of discarding the Japanese effect of the toxin. What is more, because of 1 Kataoka S, Hori A, Shirakawa T, et al. experience, an inquiry as to why the age the severe general disability following his Paramedian pontine infarction. Neurological/ distributions are so different seems appropri- , this patient was the ideal subject for topographical correlation. Stroke ate. 28 such treatment: by injecting his last working 1997; :809–15. 2 Miller NR. Topical diagnosis of neuropathic H B Gardner muscle we produced an artificial impairment ocular motility disorders. In: Miller NR, ed. of the vestibulo-ocular reflex, which generates Manitou Springs, CO, USA; Walsh and Hoyt’s clinical [email protected] eye movements to compensate for head neuro-ophthalmology. 4th ed. Baltimore: perturbations. Paralysing eye movements Williams & Wilkins, 1985;2:712–15. Accepted for publication 17 November 2002

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but evidence of pigment clumps on the ante- Br J Ophthalmol: first published as 10.1136/bjo.87.7.918-a on 1 July 2003. Downloaded from Table 1 Age distributions rior capsule in each eye. The right crystalline showed dense nuclear sclerosis and Age (months) posterior subcapsular cataractous change. Funduscopic examination demonstrated a 12345678910111213141516 cup to disc ratio of 0.7 in the right eye. The Number Kivlin 9 13 18 15 6 10 7416333121 disc, macula, and vessels were normal except of cases Aoki0011116625201000 for mild arteriolar narrowing. The examina- Ikeda 0000003133110011 tion of the left eye was significant for venous congestion with a small superficial nerve fibre layer haemorrhage on the inferior border of the disc. This possibly represented an impend- ing vein occlusion. Although it was believed that Table 2 Probabilities surgery could be done safely without address- ing the management of the angiomas, the risk t value Degrees of freedom Probability of lasering the angiomas was low and if closure of the vascular loops was achieved, the Aoki = Ikeda 0.79 13 >0.200 intraoperative risk for bleeding might be Ikeda = Kivlin 3.43 13 <0.0025 reduced. The patient was taken off aspirin Aoki = Kivlin 4.66 25 <0.0005 before the laser treatment and an angio- A + I = Kivlin 6.09 39 <0.000001 gram was performed to guide treatment in order not to miss any subclinical leaking vas- cular tufts (Fig 3). Argon laser was used with 200 µm spot size, power of 200 mW for 0.1 second duration. A total of 50 spots were administered to close all tufts appreciated prednisolone acetate 1% (Falcon Pharmaceu- References clinically and angiographically. No bleeding 1 Aoki N, Masuzawa H. Infantile acute ticals, Fort Worth, TX, USA) four times a day was noted during the procedure. The patient subdural hematoma. Clinical analysis of 26 for 1 week to decrease light sensitivity and to subsequently underwent uncomplicated ext- cases. J Neurosurg 1984;61:273–80. prevent intraocular inflammation. The hy- racapsular cataract extraction through a clear Rekate HL J 2 . Subdural hematomas in Infants. phaema subsequently resolved without se- corneal incision under topical anaesthesia. Neurosurg. 1985;62:316–17. quelae. It was suggested that if he suffered a 3 Ikeda A, Sato O, Tsugane R, et al. Infantile Upon insertion of the intraocular lens, a small rare occasional haemorrhage he would be amount of blood was noticed in the anterior acute subdural hematoma. Child’s Nerve Syst treated symptomatically, but multiple repeat 1987;3:19–22. chamber, most probably secondary to iris 4 Kivlin JD. A 12-Year ophthalmologic haemorrhages would be treated with laser trauma during the manoeuvre. This was experience with the shaken baby syndrome at coagulation or surgical excision. washed out with balanced salt solution. No a regional children’s hospital. Trans Am He now presents to the , cataract, blood was noticed in the anterior chamber on Ophthalmol Soc 1999;97:545–581. and refractive service at the Wilmer Eye Insti- the first postoperative day nor during a 10 5 Ommaya AK, Goldsmith W, Thibault L. tute for reduced visual acuity primarily in the month postoperative follow up period. Biomechanics and neuropathology of adult right eye. On examination, Snellen visual and paediatric head injury. Br J Neurosurg acuity measured 20/400 in the right eye with Comment 2002;16:220–42. Vascular anomalies of the pupillary margin Uscinski R an intraocular pressure measuring 15 mm Hg. 6 . Shaken baby are rarely seen but have been previously syndrome:fundamental questions. Br J were round and reactive without an Neurosurg 2002;16:217–19. afferent pupillary defect. External examina- implicated as a possible cause of spontaneous tion was significant for multiple 1–2 mm hyphaema.3 More unusual are iris haemangi- http://bjo.bmj.com/ raised cutaneous haemangiomas on the chest, omas associated with cutaneous haemangi- Treatment of vascular tufts at the neck, and back (Fig 1). The lesions were pain- omas. Generalised cutaneous and visceral pupillary margin before cataract less to touch, and according to the patient, surgery have been increasing in number since child- hood yet hadn’t increased in size, changed Iris vascular tufts or microhaemangiomas are colour, nor caused bleeding. Slit lamp biomi- an infrequent finding on ophthalmic evalua- croscopic examination was significant for tion. Previous reports have attributed vascular multiple small vascular loops along the - tufts at the papillary margin of the iris to lary margin of the iris in each eye (Fig 2). on September 28, 2021 by guest. Protected copyright. diabetes, myotonic dystrophy,1 in association Gonioscopic examination showed no neovas- with Sturge-Weber syndrome,2 or in associ- cularisation of the anterior chamber angle. ation with haemangioma of the or After dilatation, there was no active bleeding . We describe a patient with multiple cutaneous and iris margin haemangiomas who had a history of recurrent hyphaema and underwent successful argon laser treatment of pupillary margin haemangiomas before Figure 2 Slit lamp biomicroscopic image of extracapsular cataract extraction with in- pupillary margin vascular loops (arrows). traocular lens implantation. Case report The patient is a 75 year old man first seen 2 years earlier by the retinovascular service at the Wilmer Eye Institute, Baltimore, MD, USA, for recurrent hyphaema in the left eye. He was noted to have multiple haemangiomas on the pupillary border of both eyes as well as numerous cutaneous haemangiomas on his trunk. A small hyphaema was appreciated inferiorly in the left eye with no active bleed- ing. Gonioscopic examination was normal except for blood in the inferior angle and the intraocular pressure was 16 mm Hg in each eye. There was no corneal endothelial blood staining. He was treated with homatropine hydrobromide ophthalmic solution 5% (Ciba Figure 1 Multiple cutaneous Figure 3 Iris angiogram showing multiple Vision, Duluth, GA, USA) twice a day and haemangiomas on the trunk. leaking vascular tufts at the pupillary margin.

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7 Hagen AP, Williams GA. Argon laser haemangiomas have been described as diffuse Br J Ophthalmol: first published as 10.1136/bjo.87.7.918-a on 1 July 2003. Downloaded from congenital haemangiomatosis in neonates,4 treatment of a bleeding iris vascular tuft. Am J but iris and cutaneous haemangiomas in Ophthalmol 1986;101:379–80. adults are infrequently described. 8 Maner RS, Sachs W. Spontaneous . 74 Vascular tufts at the pupillary margins are Am J Ophthalmol 1972; :293–5. usually asymptomatic and if hyphaema does occur, recurrence is unlikely.5 Past treatment Treatment of retinal folds using had been reserved for patients with recurrent a modified macula relocation hyphaema or bleeds recalcitrant to medical management. Argon laser treatment of a technique with perfluoro- bleeding iris vascular tuft has been described hexyloctane tamponade twice previously for active bleeding resulting in hyphaema with increased intraocular pres- Retinal folds are a relatively uncommon com- sure. In both case reports, few laser applica- plication of retinal surgery. Macula involve- tions easily stopped the haemorrhaging.67Our ment can produce poor acuity and disturbing patient suffered recurrent hyphaemas in one metamorphopsia. We report a novel treatment eye and presented with a mature cataract in for macula fold using the surgical techniques the other. Surgical decompression of the , of foveal translocation and perfluorohexy- surgical manipulation causing trauma to the loctane (F6H8), a new heavier than water fragile vascular loops, hypotony, and frequent agent licensed for long term internal 12 postoperative use of mydriatics causing pupil- tamponade. lary “gymnastics” can all cause haemorrhage Case report Figure 2 Perfluorohexyloctane displaces in patients with otherwise asymptomatic vas- subretinal fluid anteriorly, putting the 8 A 51 year old man with Terson’s syndrome cular tufts. Although no previous study dem- on stretch, and ironing out the fold. onstrated bleeding of the fragile vascular tufts was found to have on with surgical decompression, it was theorised B-scan ultrasonography. He underwent vitrec- that closure of the haemangiomas would tomy and lensectomy with C2F6 gas tampon- folds include superior bullous detachment, reduce the intraoperative risk of bleeding dur- ade for a superior, macula off retinal detach- gas tamponade (bubble large in relation to ing cataract surgery. The major risk of the laser ment. He was postured face down overnight. detachment), circumferential buckles, and was bleeding during the procedure, but this A retinal fold crossing the macula was noted incomplete drainage of SRF. When gas tam- was considered low compared to a possible on the first postoperative day (Fig 1A). At 3 ponade is used in the presence of residual SRF bleeding process during surgery because a months the best corrected acuity was 6/24. starting the posturing with the break depend- closed eye procedure would allow for a more The patient described the image in the ent and slowly rolling the patient to the rapid tamponade of any bleeding process. affected eye as being split diagonally, with the desired posture may reduce the risk of macula Another risk was the possible damage to the two half images separated. He was referred to folds. Larrison et al4 reported that out of 15 lens that would be extracted in any case. Other our unit for further management. laser risks were intraocular inflammation due We used a 41 gauge needle to detach cases with folds involving the macula one to iris or lens damage and glaucoma, which approximately one quarter of the retina by third had postoperative acuity of 6/60 or worse 3 and only one third managed 6/18 or better can be caused by an inflammatory process or saline infusion into the subretinal space. F6H8 was injected displacing subretinal fluid (SRF) (mean follow up 25 months). Recent data the result of hyphaema. 7 We observed only minimal bleeding from anteriorly, opening out the retinal fold and from a dog model of macula relocation the iris during cataract surgery and no further reapposing the photoreceptors to the pigment suggest that macula folds may be associated hyphaema in the postoperative period and epithelium. No direct retinal manipulation with progressive visual deterioration. Hayashi therefore recommend considering argon laser was required. The SRF was left in situ and the et al demonstrated progressive loss of photore- treatment to pupillary margin vascular tufts patient postured on his back to allow the ceptors and thinning of the outer nuclear before surgery to decrease the possibility of retina to “iron out” slowly as the SRF layer within retinal folds. TUNEL assay http://bjo.bmj.com/ showed apoptotic cells in the outer and inner intraoperative and well as postoperative com- resorbed. The F6H8 was removed after 5 days. plications of uncontrolled haemorrhaging. The retina remained flat, without folds (Fig nuclear layers of the folds. 1B). Seven weeks after surgery his metamor- Perfluorohexyloctane is a semi-fluorinated Financial interest: none. phopsia had resolved with a best corrected alkane with a specific gravity of 1.35, and a M Winnick, E Margalit, A P Schachat, acuity of 6/18+2. high interfacial tension to water (49 mN/m). Its use in complicated retinal detachment W J Stark Electroretinography was performed before and 10 weeks after surgery using ISCEV surgery and the histology of associated Cornea, Cataract and Refractive Service and the 28 standard protocol. The ERG responses showed epiretinal membranes have been reported.

Retinal Vascular Center, Wilmer Eye Institute, Johns on September 28, 2021 by guest. Protected copyright. Hopkins University School of Medicine, Baltimore, no evidence of diminution following rede- We have previously demonstrated that the retina can be stretched by brushing, a phenom- MD, USA tachment and subsequent removal of F6H8 tamponade. (Standard flash in dark adapted enon we referred to as redistribution of neuro- 3 Correspondence to: Walter J Stark, MD, Corneal state gave a-wave amplitudes of 195 µV before sensory retina. Macular translocation can be and Cataract Services, Wilmer Eye Institute, 327 surgery and 219 µV after; b-wave amplitudes achieved without imbrication to gener- 9 Maumenee Building, 600 N. Wolfe Street, of 367 µV before and 453 µV after.) ate redundancy, by introducing a gas bubble in Baltimore, MD 21287-9238, USA; the presence of a bullous retinal detachment. [email protected] Comment The bubble occupies the top half of the vitreous Accepted for publication 19 November 2002 Retinal folds through the macula have been cavity. The SRF is displaced inferiorly and, con- reported following both vitrectomy4 and con- fined by the anterior attachment of retina, puts References 5 ventional surgery for retinal detachment. Van the macula on stretch. 1 Cobb B, Shilling JS, Chisholm IH. Vascular Meurs et al report the incidence as 2.8% with Similarly, in our patient, we induced a bul- tufts at the pupillary margin in myotonic conventional surgery.6 Risk factors for retinal lous retinal detachment, used a bubble of dystrophy. Am J Ophthalmol 1970;69:573–82. 2 Reese AB. Tumors of the eye. 3rd ed. New York: Harper & Row, 1976:282. 3 Dahlmann AH, Benson MT. Spontaneous hyphema secondary to iris vascular tufts. Arch Ophthalmol 2001;119:1728. 4 Naidoff MA, Kenyon KR, Green WR. Iris hemangioma and abnormal retinal vasculature in a case of diffuse congenital hemangiomatosis. Am J Ophthalmol 1971;72:633–44. 5 Podolsky M, Srinivasan BD. Spontaneous hyphema secondary to vascular tuft of pupillary margin of the iris. Arch Ophthalmol 1979;97:301–2. 6 Coleman SL, Green WR, Patz A. Vascular tufts of pupillary margin of iris. Am J Figure 1 Fundus photograph showing macula fold before surgical correction (A), and 7 Ophthalmol 1977;83:881–3. weeks after correction (B).

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heavy liquid and postured the patient supine. Br J Ophthalmol: first published as 10.1136/bjo.87.7.918-a on 1 July 2003. Downloaded from

The F6H8 occupied the dependent part of the vitreous cavity and displaced the SRF periph- erally and anteriorly. The SRF is confined by the attachment of the retina at the ora serrata. This effectively put the retina on stretch and “ironed out” the macular fold (Fig 2). Kertes and Peyman10 reported treatment of retinal folds in two patients having surgery for tractional retinal detachment (one diabetic, one toxocara granuloma). They used per- operative perfluoro-perhydrophenanthrene tamponade and direct retinal manipulation with a silicone tipped cannula. No significant visual improvement was noted as the folds were outside the macula. Our technique involves no direct instrumental manipulation of the central retina. We have been able to effectively treat the macula fold by exploiting the specific gravity of the tamponade agent. Avoidance of macula folds by addressing causative factors is obviously preferable to treatment. We have been impressed with the complete disappearance of the fold in this case. In selected cases surgery may be appro- priate to alleviate troublesome metamorphop- sia and possibly reduce the risk of permanent and progressive reduction in vision resulting from the macular fold.

E N Herbert, C Groenewald, D Wong Figure 1 (A) Lower third of the left cornea showing a slightly elevated, yellowish, Royal Liverpool University Hospital, Prescott Street, subepithelial and sharply demarcated opacity. Note the separation of the opacity from the Liverpool L8 7NP, UK limbus (arrow), attenuated by pronounced vessels. (B) Histological section of the superficial Correspondence to: Edward N Herbert, Royal cornea, showing a diffuse hyalinosis of the stroma (zone of marked hyalinosis denoted by Liverpool University Hospital, Prescott Street, arrowheads; haematoxylin and eosin). (C) Electron micrograph of the removed corneal stroma Liverpool L8 7NP, UK; [email protected] showing many fibrillar structures, partly arranged in bundles, representing collagen tissue. (D) Recurrent with characteristic nodular lesions (b), showing an extension along Accepted for publication 4 December 2002 the nasal limbus with the start of corneal vascularisation (asterisk). Note significant increase in References limbal involvement in comparison with (A). (E) Cornea of the right eye showing a punctual, superficial opacity in paracentral location. 1 Zeana D, Becker J, Kuckelkorn R, et al. Perfluorohexyloctane: a long term vitreous tamponade in the experimental animal. Int keratopathy, or spheroidal degeneration of the was markedly different, consisting of several, Ophthalmol 1999;23:17–24. 2 2 Kirchhof B, Wong D, van Meurs J, et al.Use cornea. A literature search failed to reveal any peripheral, subepithelial, white, slightly cases of initially diagnosed hyaline degenera- prominent lesions. The corresponding juxta-

of perfluorohexyloctane as a long-term internal http://bjo.bmj.com/ tamponade agent in complicated retinal tion of the cornea as a precursor of Salz- limbal cornea was characterised by cloudy detachment surgery. Am J Ophthalmol mann’s corneal degeneration. We present the opacification and the start of vascularisation 2002;133:95–101. first case known to us of initially diagnosed (Fig 1D). The cornea of the right eye, which 3 Wong D, Lois N. Foveal relocation by hyaline degeneration of the cornea, assumed was without pathological findings 2 years redistribution of the neurosensory retina. Br J to be a precursor of Salzmann’s corneal earlier, now exhibited a circumscribed injec- Ophthalmol 2000;84:352–7. 4 Larrison WI, Frederick AR Jr, Peterson TJ, et degeneration. tion of limbal vessels as well as a punctiform, superficial opacity at a paracentral location al. Posterior retinal folds following vitreoretinal Case report surgery. Arch Ophthalmol 1993;111:621–5. (Fig 1E). The described findings were un-

5 Pavan PR. Retinal fold in macula following A 34 year old woman was referred to our changed at the time of the most recent exam- on September 28, 2021 by guest. Protected copyright. intraocular gas. Arch Ophthalmol department in April 1998 with increasing ination of the patient in August 2002. The 1984;102:83–4. opacity of the left cornea. Her medical and clinical aspect of the left eye and the bilateral 6 Van Meurs JC, Humalda D, Mertens DA, et ophthalmological history was uneventful. The occurrence of corneal disease enabled the al. Retinal folds through the macula. Doc lower third of the left cornea showed a slightly diagnosis of Salzmann’s corneal degenera- Ophthalmol 1991;78:335–40. elevated, yellowish, subepithelial opacity, Hayashi A tion. 7 , Usui S, Kawaguchi K, et al. sharply demarcated and separated from the Retinal changes after retinal translocation Comment surgery with scleral imbrication in dog eyes. limbus by a marked interspace (Fig 1A). The Invest Ophthalmol Vis Sci 2000;41:4288–92. right eye was without pathological findings. The diagnosis of Salzmann’s corneal degen- 8 Hiscott P, Magee RM, Colthurst M, et al. The corneal opacity was removed by a scarifier eration is made clinically, with subepithelial, Clinicopathological correlation of epiretinal both because of persistent foreign body prominent corneal lesions representing the membranes and posterior lens opacification sensation and for diagnostic purposes. most important sign of this disease.3 following perfluorohexyloctane. Br J The histological examination of the re- We believe that the initial corneal altera- Ophthalmol 2001;85:179–83. moved corneal tissue revealed marked, diffuse tion, clinically diagnosed as hyaline degenera- De Juan E Jr 9 , Vander JF. Effective macula hyalinosis of the stroma (Fig 1B), and focal tion of the cornea, represents a precursor of translocation without scleral imbrication . Am J Ophthalmol 1999;128:380–2. degenerations of the overlying corneal epithe- Salzmann’s corneal degeneration. This as- 10 Kertes PJ, Peyman GA. Management of dry lium. The presence of amyloid substance was sumption is based on the fact that the respec- retinal folds. Int Ophthalmol 1997;21:53–5. excluded by Congo red staining. Electron tive histological findings already indicated the microscopy demonstrated the described hya- presence of this pathology.4–6 In the region of line areas to represent collagenous tissue (Fig nodular thickening the superficial stromal Is hyaline degeneration of the 1C). The assessment of the clinical and histo- tissue consists of collagen fibrils which are cornea a precursor of Salzmann’s logical appearance of the corneal changes led hyalinised and arranged in an irregular fash- corneal degeneration? to the diagnosis of hyaline degeneration of the ion in the absence of inflammatory changes or cornea, according to the classification of Smo- vascularisation. The corneal epithelium shows Hyaline degeneration of the cornea has been lin and Thoft.1 focal degenerations, while Bowman’s mem- described by Smolin and Thoft1 as a specific After a period of 2 years the patient brane is not identified at its usual subepithe- and rare pathological entity. Other authors presented with recurrent corneal opacity lial location. have used the term hyaline degeneration of extending beyond the initial pathological This case gives rise to the question as to the cornea synonymous with climatic droplet area. The clinical appearance of the opacity whether hyaline degeneration may exist as a

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separate entity. Furthermore, if hyaline de- Comment Br J Ophthalmol: first published as 10.1136/bjo.87.7.918-a on 1 July 2003. Downloaded from generation of the cornea is considered to be a This patient has unfortunately had infection precursor of Salzmann’s corneal degenera- of the cornea with virus, bacteria, and fungus. tion, the apparently spontaneous develop- The previous herpetic and rosacea related ment of this condition in this case does not keratopathy resulted in his original corneal conform to this description. The published grafts and were a risk factor for the develop- cases of Salzmann’s corneal degeneration are ment of bacterial . Considerable almost without exception associated with a demolition and construction work was taking history of chronic or recurrent place at the time the patient was admitted to keratoconjunctivitis347 and, less frequently, the Royal Devon and Exeter Hospital. The old with repeated surgical trauma8 or corneal hospital tower block was being pulled down dystrophy.89 The spontaneous occurrence of and the aspergillus infection was probably Salzmann’s corneal degeneration we report due to contamination from fungal spores has only rarely been described.358 A possible released during the demolition work. explanation for this may be that two variants Penetrating keratoplasty is a recognised of Salzmann’s corneal degeneration exist: a treatment for ,5 although the secondary variant, associated with different graft was performed for the corneal perfora- corneal pathologies, and a primary one. tion and the fungal infection was only noted Figure 1 with . Further work is required to determine after the graft. We believe this is the first whether the aetiology of the primary variant documented combined bacterial and fungal might be related to limbal insufficiency, which keratomileusis.23 is also a keratitis in the United Kingdom that may be eventually causes both eyes to be affected, as rare event after trauma or surgery. Endo- attributed to contamination by fungal spores is suggested by the onset of clinical signs of genous aspergillus endophthalmitis is seen in released by hospital demolition work. corneal conjunctivalisation in our patient.10 patients who are immunocompromised, have B Burt, G Pappas, P Simcock endocarditis, or a history of injecting drug M Frising, S Pitz, D Olbert West of England Eye Unit, Royal Devon and Exeter Department of Ophthalmology, Johannes use. An outbreak of ocular aspergillosis Hospital, Exeter EX2 5DW, UK Gutenberg-University, Langenbeckstrasse 1, following cataract surgery has been reported D-55101 Mainz, Germany in association with building a new hospital in Correspondence to: Peter Simcock, West of the Middle East.4 We report a case of aspergil- England Eye Unit, Royal Devon and Exeter J Kriegsmann lus keratitis associated with hospital con- Hospital, Barrack Road, Exeter EX2 5DW, UK; Institute of Pathology, Moltkestrasse 32, D-54292 struction in the United Kingdom. [email protected] Trier, Germany Case report Accepted for publication 4 December 2002 W Lisch A 43 year old man presented with a right Municipal Hospital Hanau, Leimenstrasse 20, References sided corneal ulcer and a vision of hand D-63450 Hanau, Germany Mendicute J movements (Fig 1). He had a past history of 1 , Orbegozo J, Ruiz M, et al. Keratomycosis after cataract surgery. J Correspondence to: M Frising; bilateral , rosacea Cataract Refract Surg 2000;26:1660–6. [email protected] related keratopathy, bilateral corneal grafts, 2 Kuo IC, Margolis TP, Cevallos V, et al. and cataract surgery. The right corneal ulcer Aspergillus fumigatus keratitis after laser in situ Accepted for publication 4 December 2002 was treated with intensive topical ofloxacin keratomileusis. Cornea 2001;20:342–4. References and prednisolone acetate 1%. Alpha haemo- 3 Ritterband D, Kelly J, McNamara T, et al. Delayed-onset multifocal polymicrobial 1 Smolin G. Corneal dystrophies and lytic streptococci and coagulase negative staphylococci were cultured from the corneal keratitis after laser in situ keratomileusis. J degenerations. In: Smolin G, Thoft RA, eds 28 scrape. The central cornea thinned and a Cataract Refract Surg 2002; :898–9. The cornea. 3rd ed. Boston, New York, 4 Tabbara KF, Al Jabarti A. Hospital Toronto, London: Little, Brown, 1994:503. hypopyon became visible. The cornea then construction-associated outbreak of ocular http://bjo.bmj.com/ 2 Gray RH, Johnson GJ, Freedman A. Climatic perforated and a bandage contact lens and Aspergillosis after cataract surgery. droplet keratopathy. Surv Ophthalmol glue was placed on the cornea while graft Ophthalmology 1998;105:522–6. 1992;36:241–53. material was being obtained. A penetrating 5 Xie L, Dong X, Shi W. Treatment of fungal 3 Salzmann M. Über eine Abart der keratoplasty was performed witha9mm keratitis by penetrating keratoplasty. Br J knötchenförmigen Hornhautdystrophie. Ztschr Ophthalmol 2001;85:1070–4. Augenheilkd 1925;57:92–9. donor placed into an 8.5 mm recipient bed 4 Vannas A, Hogan M, Wood I. Salzmann’s with interrupted sutures (Fig 2). Soon after nodular degeneration of the cornea. Am J surgery the microbiology laboratory grew Thyroid : an unusual Ophthalmol 1975;79:211–19. Aspergillus fumigatus from two plates from the 5 Muir E. Salzmann’s nodular corneal corneal scrape. The patient was taken back to presentation on September 28, 2021 by guest. Protected copyright. dystrophy (report of a case). Am J Ophthalmol theatre for intravitreal amphotericin B injec- 1940;23:138–44. Viagra (Sildenafil) is an oral preparation for tion and topical amphotericin was com- the treatment of male erectile dysfunction. 6 Bischler V. Dystrophie cornéenne nodulaire menced. The patient made an excellent recov- de Salzmann. Ophthalmologica Although the drug is marketed solely for its ery and has maintained a vision of 6/9 in the 1946;111:111–19. − therapeutic purposes, it has high potential for 7 Hanselmayer H. Knötchenförmige right eye with a refraction of 3.25/ × abuse owing to its ability to intensify and pro- Hornhautdystrophie nach Salzmann. Klin +3.00 105. long erectile response. We describe here an Monatsbl Augenheilkd 1968;153:833–7. ocular side effect following its use as a recrea- 8 Wood TO. Salzmann’s nodular degeneration. tional drug, which led to the diagnosis of thy- Cornea 1990;9:17–22. 9 Werner Leonardo P, Issid K, Werner Liliana roid eye disease. P, et al. Salzmann’s corneal degeneration associated with epithelial basement Case report membrane dystrophy. Cornea A 30 year old white man was referred to the 2000;19:121–3. eye clinic, with a history of waking up one 10 Kruse FE, Völcker HE. Die Stammzellen des morning with a left proptosis, having had no Hornhautepithels am Limbus. Physiologie und ocular signs or symptoms the previous day. Bedeutung für Hornhauterkrankungen. In: The patient did not have any subjective symp- Kampik A, Grehn F, eds. Das äussere Auge. toms of pain, redness, change in visual acuity, Stuttgart: Enke, 1996:70. double vision, or of hearing any sounds. There was no history of direct or indirect trauma. He Hospital acquired aspergillus gave a history of having acquired a tablet of keratitis Viagra from a friend at a Christmas party. He ingested half and gave half to his partner. The Aspergillus fumigatus is a ubiquitous mould exact dosage strength was unknown. His that rarely causes ocular pathology. Aspergil- partner noticed increased visibility of the lus keratitis may be seen following trauma white of the eye under the left upper lid. He or surgery1 to the eye and has recently Figure 2 Corneal graft 1 month after was otherwise healthy and was taking no been reported following laser in situ surgery. medication.

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Correspondence to: Jai Shankar, Royal Liverpool

Visual acuity was 6/5 unaided in each eye. Br J Ophthalmol: first published as 10.1136/bjo.87.7.918-a on 1 July 2003. Downloaded from Ocular examination showeda3mmaxial University Hospital, Prescot Street, Liverpool L7 8XP, non-pulsatile left proptosis. He was ortho- UK; [email protected] phoric and ocular movements were unre- Accepted for publication 9 December 2002 stricted. Anterior segment examination showed generalised conjunctival engorge- References ment on both sides, more on the left than the 1 Marmor MF, Kessler R. Sildenafil (Viagra) right. Pupils were normally reacting and fun- and ophthalmology. Surv Ophthalmol dus examination was unremarkable. In- 1999;123:153–62. traocular pressure was normal with no sig- 2 Gabrieli CB, Regine F, Vingolo EM, et al. nificant difference between straight gaze and Subjective visual haloes after sildenafil: up gaze. Auscultation over the globe revealed electroretinographic evaluation. no bruit. Ophthalmology 2001;108:877–81. Vobig MA The clinical findings along with the acute 3 , Klotz T, Staak M, et al. Retinal side effects of sildenafil (Letter). Lancet onset history led us to suspect superior 1999;353:375. ophthalmic vein thrombosis as a possible 4 Grunwald JE, Siu KK, Jacob SS, et al. Effect cause. An magnetic resonance imaging (MRI) of sildenafil citrate (Viagra) on the ocular scan was ordered with a specific request to circulation. Am J Ophthalmol Figure 1 External photograph of the left comment on the calibre of the superior 2001;131:751–5. eye before treatment with campath-1H. Note ophthalmic veins. The MRI scans showed 5 Egan R, Pomeranz H. Sildenafil (Viagra) the severe injection and the glue applied normal superior ophthalmic veins bilaterally associated anterior ischaemic optic nasally. but thickening of all extraocular muscles, par- neuropathy. Arch Ophthalmol 2000;118:291–2. ticularly the inferior recti on both sides. The 6 Donahue SP, Taylor RJ. Pupil-sparing third inferior rectus was intensely white on T2 nerve palsy associated with sildenafil citrate with prednisolone, cyclosporin A and myco- weighted scans. Biochemical tests for thyroid (Viagra). Am J Ophthalmol 1998;126:476–7. phenolate mofetil, topical prednisolone and function showed him to have high T3 and T4 cyclosporin A, and oral doxycycline, the levels and very low TSH levels. Mooren’s ulcer resolved with inflammation and corneal melting continued to advance. Corneal microperforations were Comment campath-1H treated with two consecutive applications of Sildenafil citrate has been in use since early histoacrylic glue (see Fig 1). Mooren’s ulcer is a rare idiopathic peripheral 1998 for the treatment of male erectile A 5 day course of campath intravenously ulcerative keratitis. The diagnosis is usually dysfunction. It is a selective cyclic guanosine was then administered. After the first week, based on characteristic clinical features and monophosphate dependent phosphodieste- there was marked decrease of the corneal absence of other causes of peripheral keratitis. rase type 5 (PDE5) inhibitor. It potentiates the inflammation, with epithelial healing and The clinical course can be unremitting, smooth muscle relaxant effect of nitric oxide improvement of pain and . Im- particularly in bilateral disease, occasionally and leads to engorgement of the sinusoids of 12 munosuppression was reduced to a low dose leading to total loss of stroma. the corpus cavernosa with a resultant penile of oral and topical prednisolone. Two months An autoimmune process is recognised as erection. At the time of orgasm, emission, and later, a minor recurrence was treated with oral being central to the pathogenesis. ejaculation sympathomimetic substances— mycophenolate mofetil and topical cyclo- Calgranulin-C (CaGC), produced by granu- adrenaline (epinephrine) and noradrenaline sporin A. The cornea healed within a week locytes and also expressed by keratocytes, (norepinephrine)—are released with conse- with no further corneal inflammation and appears to be the target protein for the quent sinusoidal smooth muscle contraction loss of stroma. 1 autoimmune response that leads to Mooren’s and rapid loss of penile rigidity. 2 The patient had a transient anaemia, reduc- ulcer. Previous corneal trauma and a higher As with any new drug, clinical information tion in both T and B cell counts and reversal of prevalence of HLA class II subtypes have been and known side effects with regard to CD4:CD8 ratio. A posterior subcapsular cata- http://bjo.bmj.com/ associated with Mooren’s ulcer. sildenafil are limited. Ocular side effects are ract developed, operated on 10 months after The disease responds to immunosuppres- few. Although sildenafil was developed as a campath-1H treatment. Fourteen months sion with variable success. Surgical treat- selective PDE5 inhibitor, it has about 10% later, the eye remained quiet with a stable ments such as conjunctival recession have effect against PDE6—an enzyme localised in ocular surface and corneal stroma, and visual been proposed. Campath-1H is a humanised retinal photoreceptors. This results in various acuity of 20/25. His immunosuppression was lymphocytotoxic monoclonal antibody (mAb) visual symptoms like a blue tinge to vision, being tapered gradually. that targets the CD52 antigen on T lym- impaired colour vision, increased light sensi- phocytes. Successful mAb therapy using tivity, and blurred vision. Symptoms are tran- Comment

campath-1H has been reported in serious on September 28, 2021 by guest. Protected copyright. sient and occur between 2–4 hours after ophthalmic inflammatory conditions that In this patient with severe Mooren’s ulcer ingestion. Results of ocular electrophysiologi- standard treatments including conjunctival 23 were unresponsive to maximum conventional cal tests have been variable. A recent study immunosuppression.1–5 recession and aggressive triple immunosup- showed no effect of sildenafil on mean blood pression did not control the disease. Treat- pressure, intraocular pressure, perfusion pres- Case report ment with campath-1H was successful. Al- sure, or choroidal and head blood A 36 year old man presented to the eye though medium term tolerance appears to be flow,4 but there have been isolated reports of department with a severe alkaline burn in excellent, long term risks of infection and anterior ischaemic ,5 vascular both eyes. The right eye had severe stromal malignancy are still to be determined. third nerve palsy,6 and retinal vascular occlu- opacity and 360 degree limbal ischaemia, and Campath-1H may be considered a last resort sions. was enucleated 2.5 years later after multiple drug for use in those patients with Mooren’s Lid retraction following ingestion of Viagra surgical treatments. The left eye had partial ulcer in whom other treatments have failed. has not been reported before. We believe that epithelial loss and inferior limbal ischaemia the release of sympathomimetic substances The authors have no commercial interests related to (four clock hours), healing completely. Visual may have produced a supranormal response the products described in the article. acuity was 20/30 a year after injury, when the in the form of noticeable lid retraction in a patient developed an inferior-nasal gutter of J van der Hoek, A Azuara-Blanco, sensitised individual with thyroid dysfunc- 160 degrees with deep and superficial vascu- tion. We speculate, based on the close tempo- K Greiner, J V Forrester larisation, with progressive discomfort and ral relation between ingestion of this recrea- Department of Ophthalmology, Aberdeen Royal photophobia, characteristic of Mooren’s ulcer. tional drug and the presentation to our Infirmary, Aberdeen, UK Autoantibodies, hepatitis titres, and tests for department, that Viagra therapy was respon- anti-filarial serology were negative. The Correspondence to: Augusto Azuara Blanco, MD sible for the unmasking of latent thyroid eye patient’s HLA (DR) profile was DR15(2), PhD, Ophthalmology Department, Aberdeen Royal disease in a sensitised individual. DR17(3), DQ6(1), DQ 2. Serum anti- Infirmary, The Eye Clinic, Foresterhill, Aberdeen AB25 2ZN, UK; [email protected] J Shankar calgranulin C determined by western blot was Royal Liverpool University Hospital, Prescot Street, not elevated. Accepted for publication 13 December 2002 Liverpool L7 8XP, UK Initial systemic and topical prednisolone with cyclosporin A failed to control the proc- References C P Noonan, P Mathew, S Hanif ess. In spite of conjunctival recession, maxi- 1 Watson PG. Management of Mooren’s Warrington General Hospital, Warrington, UK mum dose triple oral immunosuppression ulceration. Eye 1997;11:349–56.

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2 Gottsch JD, Liu SH, Minkovitz JB, et al. patient with psoriatic spondyloarthropathy choroidal neovascularisation secondary to Br J Ophthalmol: first published as 10.1136/bjo.87.7.918-a on 1 July 2003. Downloaded from Autoimmunity to a cornea-associated stromal after the initiation of etanercept therapy. punctate inner choroidopathy that failed to antigen in patients with Mooren’s ulcer. Invest Interestingly, the articular symptoms im- respond to oral corticosteroids and had poor Ophthalmol Vis Sci 1995;36:1541–7. proved in all of these five patients.9 results with submacular surgery in the 3 Taylor CJ, Smith SI, Morgan CH, et al.HLA α and Mooren’s ulceration. Br J Ophthalmol Peripheral TNF blockade by these drugs contralateral eye. leading to an increase the population of auto- 2000;84:72–5. Case report 4 Newman DK, Isaacs JD, Watson PG, et al. reactive T cells that may be myelin specific is Prevention of immune-mediated corneal graft the proposed mechanism of exacerbation of A 40 year old white female patient with punc- destruction with the anti-lymphocyte in some patients.10 A similar tate inner choroidopathy was referred to our monoclonal antibody, Campath-1H. Eye pathogenesis may explain the noted macular clinic with rapidly deteriorating 1995;9:564–9. here. Recent research demonstrates unique vision in her left eye secondary to a subfoveal 5 Dick AD, Meyer P, James T. Campath-1H cell adhesion molecules and cytokine profiles choroidal neovascularisation. She had a his- therapy in refractory ocular inflammatory tory of poor vision in the right eye following disease. Br J Ophthalmol 2000;84:107–9. in autoimmune inflammation occurring in different sites in the body.11 submacular surgery to remove a subfoveal This case report aims to create an aware- choroidal neovascular membrane. Best cor- Does etanercept induce uveitis? ness of the possibility of exacerbation of uvei- rected vision was hand movements in the tis and may warrant us to specifically look out right eye and 6/18 in the left eye. The logMAR Etanercept (Enbrel) is a fusion protein of the for uveitis in patients receiving anti-TNFα acuity in the left eye was 0.46 (38 letters mis- extracellular ligand binding portion of the therapy. read). The anterior segments and intraocular human tumour necrosis factor (TNF) receptor pressures were normal. Both fundi showed p75 and the Fc portion of human IgG1. This A R Reddy, O C Backhouse characteristic multiple pigmented atrophic agent inhibits the action of both TNFα and Leeds General Infirmary, Leeds, UK scars in the posterior pole and mid-periphery TNFγ (important pro-inflammatory cyto- in the absence of vitreous cells. There was a kines). It is being increasingly used in the Correspondence to: Aravind R Reddy, Leeds macular scar in the right eye (Fig 1). In the management of rheumatoid arthritis, psori- General Infirmary, Leeds, UK; left eye there was an elevated grey lesion with [email protected] atic arthritis, and ankylosing spondylitis with subretinal fluid and intraretinal haemor- a good outcome in both open label and Accepted for publication 13 December 2002 rhages (Fig 2A). Fluorescein angiography randomised controlled trials.1–3 Potentially confirmed a predominantly classic subfoveal References serious but uncommon adverse effects of sep- choroidal neovascular membrane (Fig 2B and α sis, reactivation of tuberculosis, worsening of 1 Braun J, Sieper J, et al. Anti-TNF therapy for C). Argon laser photocoagulation was contra- congestive cardiac failure, exacerbation of ankylosing spondylitis: international indicated because of the subfoveal location. multiple sclerosis, and reports of less serious experience. Ann Rheum Dis 2002;61(Suppl):51–60. Despitea4weekcourse of oral prednisolone skin reactions, lymphoma, autoantibodies Moreland LW (40 mg a day for 1 week then reduced by 10 4 2 , Schiff MH, Baumgartner SW, have been published. Isolated case reports of et al. Etanercept therapy in rheumatoid mg every week) the vision in the patient’s only the development of rheumatoid nodules and arthritis. A randomised controlled trial. Ann useful eye continued to worsen. The patient leucocytoclastic vasculitis with etanercept Intern Med 1999;130:478–86. refused submacular surgery because of the also exist.56We report a case of uveitis follow- 3 Gorman JD, Sack KE, Davis JC Jr. Treatment poor postoperative result in her right eye. ing etanercept treatment for ankylosing of ankylosing spondylitis by inhibition of tumor Photodynamic therapy was offered as a treat- spondylitis. necrosis factor alpha. N Engl J Med ment option. 2002;346:1349–56. After obtaining informed consent we per- Case report 4 Fleischmann R, Iqbal I, Nandeshwar P, et al. Safety and efficacy of disease-modifying formed five sessions of photodynamic therapy A 44 year old HLA B27+ve woman taking anti-rheumatic agents: focus on the benefits at 3 monthly intervals according to a standard methotrexate (15 mg weekly) and phenyl- and risks of etanercept. Drug Safety protocol. Baseline and 3 monthly post- butazone for resistant ankylosing spondylitis 2002;25:173–97. treatment logMAR visual acuities were re- of 23 years’ duration developed worsening of 5 Kekow J, Welte T, Kellner U, et al. corded and clinical and angiographic assess- arthritic symptoms. She had never suffered Development of rheumatoid nodules during http://bjo.bmj.com/ α ment was performed. After 15 months the from uveitis in the past. She was started on a anti-TNF therapy with etanercept. Arthritis Snellen acuity in her left eye has stabilised at 6 month trial of Enbrel (Immunex Corpora- Rheum 2002;46:843–4. 6 Galaria NA, Werth VP, Schumacher HR. 6/18 and her logMAR acuity is 0.2 (25 letters tion, Seattle, WA, USA) 25 mg subcutaneous Leukocytoclastic vasculitis due to etanercept. J misread). She has gained eight letters on the injections twice a week. Three weeks later she Rheumatol 2000;27:2041–4. logMAR chart and subjectively there is less presented with anterior non-granulomatous 7 De Vos AF, Van Haren MAC, Verhagen C, et distortion. Clinically, there is resolution of the uveitis in the right eye, which settled in about al. Systemic anti-tumour necrosis factor subretinal fluid and intraretinal haemor- 8 weeks with intensive topical steroids. Her antibody treatment exacerbates rhages and formation of a flat scar-like lesion endotoxin-induced uveitis in the rat. Exp Eye arthritic symptoms showed a very good (Fig 3A). Angiographically, despite some early on September 28, 2021 by guest. Protected copyright. 61 response to Enbrel. A severe flare up of joint Res 1995; :667–75. leakage, the findings are consistent with disease 8 weeks after stopping the treatment 8 Reiff A, Takei S, Sadeghi S, et al. Etanercept therapy in children with treatment-resistant reduced activity and fibrosis of the choroidal necessitated restarting Enbrel. Three weeks uveitis. Arthritis Rheum 2001;44:1411–5. neovascularisation (Fig 3B and C). An indo- later she presented with severe bilateral ante- 9 Smith JR, Levinson RD, Holland GN, et al. cyanine green angiography confirmed the rior non-granulomatous uveitis. Oral pred- Differential efficacy of tumour necrosis factor nisolone was needed to control the uveitis. inhibition in the management of inflammatory Enbrel was stopped and the uveitis resolved. A eye disease and associated rheumatic complicated cataract developed a few months disease. Arthritis Care Res 2001;45:252–7. α later and was successfully treated with IOL 10 Cope A,EttingerR,et al. The role of TNF implantation. Cystoid macular oedema in the and related cytokines in the development and function of the autoreactive T-cell repertoire. operated eye has left her with a vision of 6/18. Res Immunol 1997;148:307–12. 11 Von Andrian UH, Mackay CR. T-cell function Comment and migration: two sides of the same coin. N The close temporal association of the start of Engl J Med 2000;343:1020–34. Enbrel treatment and the onset of uveitis and “challenge-rechallenge” scenario observed in Photodynamic therapy: a this patient’s uveitis suggests that Enbrel pro- voked anterior uveitis in this patient. Exacer- treatment option in choroidal bation of endotoxin induced uveitis with sys- neovascularisation secondary to temic antitumour necrosis factor antibody punctate inner choroidopathy treatment has been demonstrated in rats.7 In a Figure 1 Right eye. The photograph shows study of the efficacy of etanercept for treat- Punctate inner choroidopathy is an idiopathic the large central macular scar with retinal ment resistant juvenile idiopathic arthritic inflammatory ocular disorder characteristi- pigment hypertrophy and atrophy following uveitis in 14 children, the uveitis got worse in cally seen in young myopic women. Visual surgical removal of a choroidal one child.8 Smith et al in a retrospective analy- prognosis is generally good but sight threat- neovascularisation. Smaller circumscribed sis reported three cases of bilateral ening choroidal neovascularisation may de- pigmented atrophic scars characteristic of and one case of uveitis in patients with rheu- velop in up to 40% patients.1 We discuss verte- punctate inner choroidopathy are seen in the matoid arthritis and one case of uveitis in a porfin photodynamic therapy in subfoveal mid-periphery.

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Figure 2 Left eye at presentation. (A) The colour photograph shows a grey elevated subfoveal lesion associated with intraretinal haemorrhages and subretinal fluid and surrounding smaller atrophic pigmented lesions characteristic of punctate inner choroidopathy. (B) The arteriovenous phase of the fluorescein angiogram at 28.2 seconds shows a hyperfluorescent subfoveal choroidal neovascularisation with a typical lacy pattern and smaller punctate hyperfluorescent lesions of punctate inner choroidopathy. The area of blocked fluorescence is consistent with the intraretinal haemorrhage. (C) The late arteriovenous phase of the fluorescein angiogram at 2.09 minutes shows increased hyperfluorescence and active leakage of dye from the subfoveal choroidal neovascularisation.

Figure 3 Left eye after five verteporfin photodynamic sessions. (A) The colour photograph shows a flat subfoveal scar-like lesion with resolution of subretinal fluid and intraretinal haemorrhages. (B) The arteriovenous phase of the fluorescein angiogram at 21 seconds shows some early hyperfluorescence with reduced activity and size of the lesion. (C) The late arteriovenous phase of the fluorescein angiogram at 1.05 minute shows mainly staining of fibrosis and no active leakage. http://bjo.bmj.com/ on September 28, 2021 by guest. Protected copyright.

Figure 4 (A–C) Indocyanine green angiography of the left eye after five verteporfin photodynamic sessions at 11 seconds, 55.2 seconds, and 9.35 minutes showing no active choroidal neovascularisation and no feeder vessels.

findings of the fluorescein angiography and scars.2 Vitritis and anterior uveitis are gery has shown promising results but recur- excluded the presence of choroidal feeder ves- absent.2 Visual prognosis is good in most rence is common.4 sels that could lead to a recurrence of the neo- patients and significant visual loss is usually Photodynamic therapy using verteporfin is vascularisation (Fig 4). due to formation of choroidal safe and effective for subfoveal choroidal neo- neovascularisation.1 Choroidal neovasculari- Comment µ vascularisation in age related macular degen- sation if smaller than 100 m in diameter may eration and high .56 The verteporfin Punctate inner choroidopathy is an idiopathic resolve spontaneously.1 However, subfoveal guidelines suggested photodynamic therapy inflammatory disorder that usually occurs in choroidal neovascularisation occurs in 40% of young, myopic women.2 Both eyes are com- 1 for other aetiologies if outcome without treat- the patients. Argon laser photocoagulation is 7 monly affected. Symptoms include blurred or contraindicated for subfoveal lesions.1 Al- ment was likely to be poor. Preliminary distorted vision, light flashes, or paracentral though good results have been reported with success in ocular histoplasmosis syndrome, .2 The acute, multiple, yellow-white 1 mg/kg per day of oral prednisolone,3 the angioid streaks, idiopathic and other condi- lesions of the inner and retina of the response to oral steroids is variable if more tions has been reported.8–15 The recommended posterior pole evolve into atrophic pigmented than 200 µm in diameter.1 Submacular sur- protocol for treatment included clinical and

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57 10 Saperstein DA, Rosenfeld PJ, Bressler NM, et angiographic review every 3 months. Re- determination of the diameter of the ophthal- Br J Ophthalmol: first published as 10.1136/bjo.87.7.918-a on 1 July 2003. Downloaded from treatment was indicated if there was any al, Verteporfin in Ocular Histoplasmosis mic artery. They assume the boundaries of the fluorescein leakage from the choroidal (VOH) Study Group. Photodynamic therapy of vessel to be where detected movement starts 57 subfoveal choroidal neovascularization with neovascularisation. Retreatment was de- and ends along the m-mode line; or in other ferred if the visual acuity remained stable or verteporfin in the ocular histoplasmosis syndrome: one-year results of an uncontrolled, words the vessel boundaries are taken to be improved and the lesion fulfilled all the the positions where the grey pixels and colour 7 prospective case series. Ophthalmology following criteria : (1) minimal or no subreti- 2002;109:1499–505. pixels touch on this Doppler image. However, nal fluid on biomicroscopic examination; (2) 11 Spaide RF, Martin ML, Slakter J, et al. we are doubtful whether this definition is rel- flat scar-like appearance; (3) minimal fluores- Treatment of idiopathic subfoveal choroidal evant for the required quantitative measure- cein leakage without progression beyond the neovascular lesions using photodynamic ment. The first point is that for small vessels therapy with verteporfin. Am J Ophthalmol boundaries of the previous treatment or the width of the colour area (indicating blood involvement of the fovea. 2002;134:62–8. motion) is unfortunately relatively independ- Photodynamic therapy in this case of sub- 12 Dantas MA, Slakter JS, Negrao S, et al. Photodynamic therapy with verteporfin in ent of the true vessel diameter. The width of foveal choroidal neovascularisation secondary mallatia leventinese. Ophthalmology. to punctate inner choroidopathy was indicated the superimposed colour area is greatly influ- 2002;109:296–301. enced by the actual technical parameters used after a poor surgical result in the first eye and Valmaggia C 13 , Niederberger H, Helbig H. in colour Doppler imaging (pulse repetition the deterioration of vision in the fellow eye Photodynamic therapy for choroidal despite oral corticosteroid treatment. Five neovascularization in fundus flavimaculatus. frequency,lateral dimension of the ultrasound treatment sessions over 15 months produced Retina 2002;22:111–13. beam, colour priority, motion discriminator subjective and visual (logMAR) improvement. 14 Potter MJ, Szabo SM, Chan EY, et al. setting, colour saturation, brightness, con- Clinically there was resolution of intraretinal Photodynamic therapy of a subretinal trast, etc). Our second doubt is that, even on haemorrhages and subretinal fluid with for- neovascular membrane in type 2A idiopathic the grey scale part of the image shown by juxtafoveolar retinal telangiectasis. Am J Orge et al in their in Figure 1, no vessel wall is mation of a flat scar-like lesion. The angiogram Ophthalmol 2002;133:149–51 confirmed a stable lesion with minimal fluores- 15 Battaglia Parodi M, Da Pozzo S, Toto L, et seen, unlike the case for typical images of cein leakage, no progression beyond the al. Photodynamic therapy for choroidal large vessels like the carotid arteries. boundaries of the previous treatment and neovascularization associated with choroidal We think that because of these difficulties staining of the scar tissue. This case demon- osteoma. Retina 2001;21:660–1. regarding the determination of the vessel wall strates that verteporfin photodynamic therapy position, Orge and co-workers overestimate may be a useful treatment option in choroidal the ophthalmic artery diameter. Their diam- neovascularisation due to punctate inner MAILBOX eter estimate is 2.02 mm on average; but this choroidopathy. Further studies are needed to figure is significantly larger than is suggested confirm and support this observation. by other evidence. During conventional 10 S Chatterjee, J M Gibson MHz B-scan diagnostic examination, the oph- If you have a burning desire to respond to thalmic artery is never visible. However for Birmingham and Midland Eye Centre, City Hospital a paper published in the BJO, why not NHS Trust, Birmingham B3 2NS the dilated ophthalmic vein, in exceptional make use of our “rapid response” option? cases such as in a patient with carotideo- Correspondence to: Dr Jonathan Gibson; Log on to our website cavernous sinus fistula, or in a small baby in a [email protected] (www.bjophthalmol.com), find the paper bout of strenuous crying, the vein is then well that interests you, and send your response Accepted for publication 2 December 2002 outlined with a diameter of 1 mm or above. via email by clicking on the “eLetters” Thus, we would expecta2mmdiameter References option in the box at the top right hand artery to be clearly visible. As we demon- 1 Brown J Jr, Folk JC, Reddy CV, et al. Visual corner. strated some years ago,34 patients with a prognosis of multifocal choroiditis, punctate Providing it isn’t libellous or obscene, it pathologically dilated ophthalmic vein are inner choroidopathy, and the diffuse will be posted within seven days. You can subretinal fibrosis syndrome. Ophthalmology good candidates for non-invasive volumetric retrieve it by clicking on “read eLetters” http://bjo.bmj.com/ 1996;103:1100–5. blood flow measurement. We were able to 2 Gass JDM.In:Stereoscopic atlas of macular on our homepage. measure volumetric blood flow in the orbit of disease diagnosis and treatment. Vol 2. St The editors will decide as before patients with a high flow fistula (vein Louis: Mosby 1997:692–3. whether to also publish it in a future diameter around 3–4 mm) using the CVI-Q 3 Flaxel CJ, Owens SL, Mulholland B, et al.The paper issue. technique (Fig 1). Possibly future improve- use of corticosteroids for choroidal neovascularisation in young patients. Eye ments in spatial resolution may resolve this 1998;12(Pt 2):266–72. difficulty. 4 Olsen TW, Capone A Jr, Sternberg P Jr, et al. In a vessel like the ophthalmic artery there Subfoveal choroidal neovascularization in

Non-invasive volumetric blood is a further problem in determination of the on September 28, 2021 by guest. Protected copyright. punctate inner choroidopathy. Surgical flow measurement in the orbit average velocity, because the laminar flow in management and pathologic findings. such small vessels causes a very wide velocity Ophthalmology 1996;103:2061–9. We read with great interest the article of Orge variation within the lumen, as can be seen 5 Bressler NM. Photodynamic therapy of 1 subfoveal choroidal neovascularization in and co-workers who claim a first ever from our Figure 1. In contrast, we note that age-related with solution to the problem of non-invasive volu- the colour spectrum in the figure presented by verteporfin: two-year results of 2 randomized metric blood flow measurement in the oph- the authors is almost completely uniform and clinical trials-TAP report 2. Arch Ophthalmol thalmic artery. This is a very important topic does not show higher speed in the centre of 2001;119:198–207. both from the clinical and scientific point of the lumen compared to that close to the vessel 6 Verteporfin in Photodynamic Therapy view, since blood supply is an important Study Group wall. This might imply a relative insensitivity . Photodynamic therapy of factor, for example, in glaucoma studies. subfoveal choroidal neovascularization in of velocity discrimination within a small ves- pathologic myopia with verteporfin. 1-year However, to date for the orbital circulation sel lumen, which in addition may be of only the blood velocity has been measurable; results of a randomized clinical trial—VIP irregular cross sectional shape (that is, not 108 from this the resistivity indices can be report no 1. Ophthalmology 2001; :841–52. circular) but is only measured in one longitu- 7 Anon. Guidelines for using verteporfin calculated, but the volumetric flow cannot be dinal plane. We agree with the authors that (Visudyne) in photodynamic therapy to treat determined because the small diameter of the the analysis software is of great importance choroidal neovascularization due to orbital vessels does not allow the vessel diam- age-related macular degeneration and other eter measurement, which is indispensable for and may be a key factor in dealing with this causes. Retina 2002;22:6–18. complex situation. In spite of our reservations 8 Sickenberg M, Schmidt-Erfurth U, Miller JW, such calculation. In spite of the novelty of the report and the we, and many other workers concerned with et al. A preliminary study of photodynamic orbital circulation, are in urgent need of a reli- therapy using verteporfin for choroidal extensive analysis of the authors on the possi- neovascularization in pathologic myopia, ble sources of high variability of volumetric able solution for volumetric blood flow deter- ocular histoplasmosis syndrome, angioid flow measurements, it appears to us that there mination in the orbit. The results of Orge and streaks, and idiopathic causes. Arch are several points which need further consid- co-workers show that we are probably not far Ophthalmol 2000;118:327–36. eration; some of these were analysed in the from a definitive solution. 9 Karacorlu M, Karacorlu S, Ozdemir H, et al. 2 Photodynamic therapy with verteporfin for editorial by Hedges, but we would like to choroidal neovascularization in patients with highlight two additional questions. Acknowledgement angioid streaks(1). Am J Ophthalmol For us, a weak point of the study protocol of Supported by the Hungarian Scientific Research 2002;134:360. Orge and colleagues is their method for the Fund (OTKA T 034483).

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3 http://www.rcophth.ac.uk/publications/ Br J Ophthalmol: first published as 10.1136/bjo.87.7.918-a on 1 July 2003. Downloaded from guidelines/strabismus.html#ambly 4 Nucci P, Alfarano R, Piantanida A, et al. Compliance in antiamblyopia occlusion therapy. Acta Ophthalmol Copenh 1992;70:128–31. 5 Stewart CE, Fielder AR, Stephens DA, et al. Design of the Monitored Occlusion Treatment of Study (MOTAS). Br J Ophthalmol 2002;86:915–19. Authors’ reply We thank Sankari and colleagues for their helpful and interesting comments regarding our paper. We accept that the literature suggests a difference of1Dasadefinition of but felt the stringent definition we applied would more accurately represent a degree of anisometropia that could potentially lead to amblyopia, and therefore makes the findings more robust. The average age of the cohort was 51⁄2 years and as such the majority of tests were linear. Pure anisometropic Figure 1. CVI flowmetry of the dilated superior ophthalmic vein in a 70 year old patient amblyopia does not tend to cause as signifi- with direct carotidcavernosus sinus fistula. In the upper left image the thin white line indicates cant crowding as strabismic. We therefore felt the sonic beam-flow angle, for volume-flow calculation. The functional lumen of the vessel is that it was not necessary to equate one line of displayed in the left side of the M-mode image. Note the variation in the colour according to difference with Sheridan Gardiner to a two or the arterialisation of the circulation and the higher flow velocity in the centre of the vessel than three line difference on a linear test. Occlusion close to the wall of the vessel. The average calculated flow volume was 59.7 ml/min. regimes and compliance are always problem- atic especially in retrospective studies.1 All parents of children were given the same J Németh difference on a linear test.2 The Royal College advice and support regarding therapy and the 3 1st Department of Ophthalmology, Semmelweis of Ophthalmologists also state that on outcomes, therefore the findings of our study University, Budapest, Hungary repeated testing a difference of one line can reflect a real clinical situation. Compliance also be included—that is, 6/9 6/6. Therefore a 2 Z Harkányi, F Humml does vary with age as shown by Nucci et al, one line difference on Sheridan Gardiner may but this was significant only in the 1–2 year Department of Radiology, Heim Pal Children actually fulfil the linear criteria. old age group. There were no children of this Hospital, Budapest, Hungary The authors stated that part time occlusion age in our study. More importantly, the effect was the method of treatment. Part time of occlusion is inversely related to age, so the Correspondence to: Dr János Nemeth, 1st occlusion can vary from as much as 6 hours to Department of Ophthalmology, Semmelweis younger the child the more rapid the re- University, Tömõ u 25–29, H-1083, Budapest, 10 minutes yet the authors did not state the sponse. Most children were commenced on Hungary; [email protected] amount of occlusion to the level of vision. occlusion at their first visit after refractive Methods of occlusion have varied greatly correction, which was within 2 months of References between 1972 and 1995, so were the guide- receiving glasses. We agree that anisometropic 1 Orge F, Harris A, Kagemann L, et al. The first lines for occlusion treatment the same amblyopes may have a continuing improve- technique for non-invasive measurements of throughout the study period?

ment in their vision with just spectacle http://bjo.bmj.com/ volumetric ophthalmic artery blood flow in Furthermore ,”compliance” with treatment correction for some months.3 Depending on humans. Br J Ophthalmol 2002;86:1216–9. is recognised as an important factor affecting 2 Hedges TR. Ophthalmic artery blood flow in 3 the response to spectacle correction, this the final visual outcome in amblyopia and department will now delay occlusion for up to humans. The tortuosity and the variable course that compliance varies with age.4 The authors of the ophthalmic artery remain a problem. Br 4 months. To suggest that initiating occlusion J Ophthalmol 2002;86:1197. have not analysed if compliance varied signifi- earlier than may have been necessary would 3 Németh J, Harkányi Z. Color Doppler and cantly with age of presentation. result in a worse outcome because of poor color velocity imaging of the orbital vessels In: It has been shown that anisometropic compliance must be considered speculative. amblyopes can have improvement in vision Süveges I, Follmann P, eds. XIth Congress of In any case, failure to comply with occlusion the European Society of Ophthalmology. after a period of spectacle correction and would result in the now recommended on September 28, 2021 by guest. Protected copyright. Bologna: Monduzzi, 1997:593–6. refractive adaptation is considered an impor- treatment—that of spectacle correction alone. 4 Németh J, Süveges I, Harkányi Z. Color tant component of amblyopia treatment.5 The While there may be some debate as to the velocity imaging of orbital blood circulation. authors did not state if occlusion was started efficacy of occlusion therapy,4 there is cur- In: Hasenfratz G, ed. Ultrasound in at the first, second, or third visit after specta- rently no evidence that it is detrimental to the ophthalmology. Proceedings of the 16th cle correction. We do not know if treatment SIDUO Congress Munich, Germany 1996. final visual acuity achieved in anisometropes. Regensburg: Roderer Verlag, 2000:31–3. had been initiated prematurely and resulted in falsely increased occlusion dose, thereby C J Cobb, K Russell, A Cox, C J MacEwen giving poorer compliance. This could have Department of Opththalmology, Ninewells Hospital, “Compliance” with treatment in skewed the figures. So, we recommend exer- Dundee DD1 9SY, UK amblyopia is an important factor cising caution in interpreting the results and affecting the final visual in concluding that time at which screening is Correspondence to: Dr Alan Cox, Department of carried out, not critical in this group. Opththalmology, Ninewells Hospital, Dundee outcome DD1 9SY, UK; [email protected] P R Sankari, V Henshall, K O’Regan 1 References We discussed the article by Cobb et al with Royal Albert Edward Infirmary, Christopher Home, great interest in our journal club meeting. We Wigan Lane, Wigan WN1 2NN, UK 1 Fielder AR, Irwin M, Auld R, et al. would like to highlight some of the issues we Compliance in amblyopia therapy: objective discussed. Correspondence to: Mrs Perumal Sankari, Royal monitoring of occlusion. Br J Ophthalmol 1995;79:585–9. Evidence in the literature23 suggests ani- Albert Edward Infirmary, Christopher Home, Wigan Lane, Wigan WN1 2NN, UK; 2 Nucci P, Alfarano R, PiantanidaA, et al. sometropia is a difference of 1 DS between [email protected] Compliance in antiamblyopic occlusion both eyes but the authors use a difference of 2 therapy. Acta Ophthalmol Copenh DS. Also the minimum criteria for diagnosing References 1992;70:128–31. amblyopia on a test of visual acuity are 1 Cobb CJ, Russell K, Cox A, et al. Factors 3 Stewart CE, Fielder AR, Stephens DA, et al. accepted to be two lines difference between influencing visual outcome in anisometropic Design of the Monitored Occlusion Treatment the eyes on linear tests. However, the authors amblyopes. Br J Ophthalmol of Amblyopia Study (MOTAS). Br J 2002;86:1278–81. Ophthalmol 2002;86:915–19. use these criteria for the single optotype test 2 Ansons AM, Davies H. Amblyopia. In: 4 Snowdon SK, Stewart-Brown SL. Preschool and do not take into account the crowding Diagnosis and management of ocular motility vision screening: results of a systematic effect. A two line difference on Sheridan Gar- disorders. 3rd ed. Oxford: Blackwell Science, review. York: NHS Centre for Reviews, 1997 diner may actually equate to a three line 2001:214. (CRD Report 9).

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Can a cilio-retinal artery Br J Ophthalmol: first published as 10.1136/bjo.87.7.918-a on 1 July 2003. Downloaded from Table 1 The relation between the presence of a cilio-retinal artery and influence diabetic ? clinically significant macular oedema (CSMO) Knudsen and Lervang published an interest- No CSMO CSMO Total ing article in the BJO recently.1 The authors concluded that a cilio-retinal artery tends to No cilio-retinal artery 324 38 362 worsen diabetic but I believe Cilio-retinal artery 106 13 119 there is an alternative interpretation of the Total 430 51 481 data provided. The authors mentioned that 26/29 patients had a cilio-retinal artery in the eye with worse maculopathy, which was a sta- tistically significant result. In the results section the authors did not report whether a The authors also reported that 51 eyes had assuming all the 51 eyes with CSMO were unilateral cilio-retinal artery was present in clinically significant macular oedema from different subjects, the 2 × 2 table may the 75 subjects with identical maculopathy in (CSMO), in the group of 94 subjects with look like Table 1. This table assumes that all the right and left eyes but they stated that this 2 maculopathy. However, the χ analysis should the 104 eyes with unilateral cilio-retinal was true in all 75 subjects in the first sentence not have been performed using each eye as a artery and the 15 eyes from bilateral cilio- of the discussion. Therefore, in 75 patients the retinal cases are included, making a total of case (n=962), as it is well known that the 119 subjects with cilio-retinal arteries for cilio-retinal artery had not caused worsening right and left eyes of each patient are not of the maculopathy compared to the contra- analysis. In the above case clearly the result is independent (that is, if the right eye has not statistically significant (χ2 =0.017; lateral eye. Taken together with the 29 maculopathy, the left eye has a greater chance p>0.9). subjects with asymmetrical maculopathy, the of having maculopathy than the contralateral L Tong proportion of subjects in whom the unilateral eye of a non-affected eye in another patient). Singapore National Eye Centre, 11, 3rd Hospital cilio-retinal artery did not worsen maculopa- One possible approach would be to look at all Avenue, Singapore 168751; thy would be (75 + 3)/104 or 0.75 (95% CI the right eyes only or to randomly look at one [email protected] 0.654 to 0.827). The proportion of cases in of the two eyes of each subject and reduce n to Reference whom maculopathy was not worsened by a 481. The reader of this article will not know 1 Knudsen LL, Lervang HH. Can a cilio-retinal cilio-retinal artery was therefore significantly the outcome of this analysis without more artery influence diabetic maculopathy? Br J more than 50%. information from the authors; however, Ophthalmol 2002;86:1252–5. http://bjo.bmj.com/ on September 28, 2021 by guest. Protected copyright.

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