928 Br J Ophthalmol 2000;84:928–935

robulbar portion of the nasally. A likely is a cavernous haemangioma, but Br J Ophthalmol: first published as 10.1136/bjo.84.8.928c on 1 August 2000. Downloaded from similar but smaller mass was present in the periodic observation, rather than surgical LETTERS TO right lateral to the medial rectus muscle excision, would seem to be the best manage- (Fig 1). Both masses showed slight contrast ment. In summary, the ophthalmologist THE EDITOR enhancement. The clinical diagnosis was should include orbital cavernous haemangi- bilateral cavernous haemangioma. The left oma in the diVerential diagnosis of bilateral, as orbital mass was removed intact by a supero- well as unilateral, orbital tumours. lateral extraperiosteal approach. Gross and microscopic studies revealed a benign tumour Supported by the Eye Tumor Research Foundation, Bilateral cavernous haemangiomas of composed of large endothelial lined vascular Philadelphia, PA (J Shields, C Shields), the Noel T the orbit channels separated by fibrous stroma, consist- Sara L Simmonds Endowment for Ophthalmic ent with cavernous haemangioma (Fig 2). The Pathology, Wills Eye Hospital (RC Eagle). and from Research to Prevent Blindness (RN Hogan). EDITOR,—The great majority of orbital tu- patient had an unremarkable postoperative mours are unilateral. However, some condi- course with good visual acuity. JERRY A SHIELDS Oncology Service,Wills Eye Hospital, 900 Walnut tions, such as idiopathic orbital inflammation Street, Philadelphia, PA, 19107, USA (“pseudotumour”), granulomatous inflamma- COMMENT tion, lymphoid tumours, or metastases some- R NICK HOGAN Cavernous haemangioma of the orbit is a Wills Eye Hospital, Thomas JeVerson University, times can be bilateral. Orbital cavernous hae- common, benign tumour that almost always 12 Philadelphia, PA and the Department of mangioma is almost always unilateral. We occurs unilaterally. There are rare reports of , University of Texas Southwestern report a patient with bilateral orbital cavern- bilateral orbital cavernous haemangiomas. Medical Center, Dallas, Texas, USA ous haemangiomas that caused unilateral Fries and Char reported a case that was very CAROL L SHIELDS proptosis and visual distortion. 3 similar to ours. They excised the tumour in Oncology Service one orbit and elected to follow the asympto- RALPH C EAGLE, JR CASE REPORT matic tumour in the opposite orbit. Sullivan Department of Pathology A 37 year old man developed distorted vision and associates reported an unusual case of in the inferior field of his left eye and was multiple bilateral orbital haemangiomas.4 ROBERT H KENNEDY found to have mild left proptosis. There was Johnson and co-workers reported bilateral Wills Eye Hospital, Thomas JeVerson University, mild swelling of the left and a small orbital haemangiomas as part of MaVucci’s Philadelphia, PA and the Department of Ophthalmology, University of Texas Southwestern inferonasal visual field defect. Orbital com- syndrome, a condition characterised by en- Medical Center, Dallas, Texas, USA puted tomography (CT) revealed bilateral chondromatosis and multiple systemic orbital masses and the patient was referred to haemangiomas.5 Our patient was otherwise ARUN D SINGH the oncology service for another opinion and normal with no evidence of MaVucci’s syn- Oncology Service management. His visual acuity was 6/6 in each drome. There was also a recent report of bilat- Correspondence to: Dr Jerry A Shields eye and colour vision was normal in both eyes. eral orbital vascular masses, presumed orbital Accepted for publication 7 March 2000 The only positive findings were 3 mm of left varices, that caused intravascular papillary proptosis, mild swelling of the left optic disc, endothelial hyperplasia.6 1 Shields JA. Vasculogenic tumors and malforma- and a subtle inferonasal field defect. The The widespread use of CT and magnetic tions. In: Shields JA, ed. Diagnosis and manage- ment of orbital tumors. Philadelphia: WB Saun- orbital CT showed a round, soft tissue mass in resonance imaging to evaluate unrelated ders, 1989:123–8. the left orbit temporally that displaced the ret- problems, such as headache, has led to the 2 Shields JA, Shields CL. Vascular tumors. In: recognition of asymptomatic lesions compat- Shields JA, Shields CL, eds. Atlas of orbital tumors. Philadelphia: Lippincott Williams and ible with orbital cavernous haemangioma. We Williams, 1999:50–5. have seen several such cases and have elected 3 Fries PD, Char DH. Bilateral orbital cavernous to follow without treatment these small, haemangiomas. Br J Ophthalmol 1988;72: asymptomatic tumours, presumed to be or- 871–3. 4 Sullivan TJ, Aylward GW, Wright JE, et al. Bilat- bital cavernous haemangiomas. Conse-

eral multiple cavernous haemangiomas of the http://bjo.bmj.com/ quently, it is possible that orbital cavernous orbit. Br J Ophthalmol 1992;76:627–9. haemangioma may be more common than 5 Johnson TE, Nasr AM, Nalbandian RM, et al. previously believed. If so, additional cases of Enchondromatosis and hemangioma (MaVuc- ci’s syndrome) with orbital involvement. Am J bilateral orbital cavernous haemangioma will Ophthalmol 1990;110:153–9. probably be recognised. In our case, the 6 Shields JA, Shields CL, Eagle RC Jr, et al. Intra- asymptomatic tumour in the right orbit most vascular papillary endothelial hyperplasia with presumed bilateral orbital varices. Arch Ophthal- mol 1999;117:1247–8. on September 24, 2021 by guest. Protected copyright. Choroidal neovascularisation at a demarcation line: an immunopathological study

EDITOR,—We describe a patient presenting with a choroidal neovascular membrane (CNVM) at the demarcation line of a longstanding rhegmatogenous retinal detach- ment (RRD), and characterise its immun- opathological features following surgical re- moval.

CASE REPORT A 46 year old myopic woman attended the vit- reoretinal service with a 3 month history of a shadow in the superior half of her left visual field. Her visual acuity was 6/9 right and 6/12 left, with a of −13.0D and −9.50D eVective spheres respectively. Examination of the left fundus revealed longstanding detached and thinned inferiorly and a broad heavily pigmented demarcation line passing through the macula Figure 1 Orbital computed tomograms with Figure 2 Pathology. (A) Gross photograph of axial cut (A) and coronal cut (B), showing pseudoencapsulated reddish blue mass. (B) with associated retinal pigment epithelial bilateral circumscribed orbital soft tissue masses, Photomicrograph, showing large cavernous (RPE) hypertrophy. An area of parafoveal with a larger tumour in the left orbit and a small vascular channels typical of orbital cavernous retina adjacent to the tide mark appeared tumour in the right orbit. haemangioma (haematoxylin and eosin ×100). elevated and a fundus fluorescein angiogram

www.bjophthalmol.com Letters 929

(FFA) revealed a juxtafoveal CNVM PATHOLOGY togenous and tractional retinal detachments; Br J Ophthalmol: first published as 10.1136/bjo.84.8.928c on 1 August 2000. Downloaded from emerging from the edge of RPE hypertrophy. The CNVM specimen was fixed in 10% however, the immunopathology does not Three months later she reported decreased formol saline, processed through ascending appear to have been previously described.23 vision and metamorphopsia in her left eye, concentrations of alcohol into xylene and A demarcation line (“high watermark”) is with a best corrected left visual acuity embedded with paraYn wax. Tissue sections characteristically found in longstanding reti- reduced to counting fingers. A subfoveal 5 µm thick were freshly cut for this study, nal detachments that either progress very 4 extension of the CNVM with bordering dewaxed, and rehydrated before use. slowly or remain static. In this setting, RPE haemorrhage was present, confirmed by FFA The distribution of basic fibroblast growth cells may detach from Bruch’s membrane to (Fig 1A, B). She subsequently underwent factor (bFGF), vascular endothelial growth proliferate and undergo metaplasia in the sub- retinal space at the junction of attached and pars plana vitrectomy, parafoveal retinotomy, factor (VEGF), macrophages (PGM1), and von Willebrand factor (vWF) were investi- detached retina. Clinically, a demarcation line and removal of subfoveal CNVM, together gated using a standard biotin-streptavidin- appears as a line of increased pigmentation in with external scleral buckling, argon laser biotin, alkaline phosphatase complex method this area and may form a suYciently firm retinopexy, and 20% sulphur hexafluoride gas (Dako Ltd). The alkaline phosphatase label adhesion to prevent progression of a retinal tamponade. was visualised as a red final reaction product detachment. The local wound healing re- Postoperatively, an area of inferior retinal (Vector Ltd). Nuclei were weakly stained with sponse at the edge of the detached retina may detachment persisted and further surgery with Mayer’s haematoxylin. A normal human also lead to excessive RPE proliferation. In our silicone oil tamponade was undertaken. Sub- donor eye was used as a positive control, while patient, such chorioretinal adhesion may have sequently, a posterior subcapsular the negative control used was normal rabbit allowed the transmission of mechanical vitreo- developed and she underwent left phacoemul- serum diluted to give a final protein concen- retinal traction forces to Bruch’s membrane.3 sification with intraocular implantation tration equivalent to that of the primary anti- This could potentially have compromised the and removal of silicone oil. Postoperatively, body used. integrity of Bruch’s membrane, allowing the visual acuity improved to 6/18 and the retina Histopathological examination revealed a formation of a CNVM. High was a remained flat with no clinically apparent CNVM consisting of numerous endothelial further predisposing factor for choroidal neo- CNVM (Fig 1C). Four months later, her lined vascular channels and chronic inflam- vascularisation in this patient, making Bruch’s 1 visual acuity was reduced to 6/36. Fundal matory cells. The CNVM was lined by an membrane more susceptible to disruption. examination showed an elevated area at her incomplete layer of RPE cells on its posterior Grossniklaus and Gass have described two aspect, as determined by the clinical orienta- fovea and FFA confirmed a recurrent CNVM. fundamentally diVerent types of choroidal tion of the membrane at the time of removal We are treating this conservatively as the neovascular growth patterns—type 1, with (Fig 2A). patient is asymptomatic and has declined fur- growth of new vessels beneath the retinal pig- A large portion of the CNVM consisted of ment epithelium, and type 2, with growth of ther surgery. vascular channels lined by endothelial cells new vessels in the subsensory retinal space.5 displaying immunoreactivity for von Will- In our patient, the presence of RPE cells on ebrand antigens (Fig 2B). There was staining the posterior surface of the CNVM indicates for VEGF (Fig 2C) and bFGF (Fig 2D) in the that it represented a type 2 membrane, as extracellular matrix, with a similar distribu- determined by its clinical orientation at the tion of immunoreactivity. time of removal. Experimentally detached retina in cats has COMMENT been shown to possess higher angiogenic Choroidal neovascularisation occurs in a wide activity than normal attached retina.6 Indeed, spectrum of conditions, including degenera- peripheral retinal neovascularisation has been tive, inflammatory, traumatic, and hereditary described in chronic rhegmatogenous retinal disorders—all characterised by breaks in detachment.7 is likely to Bruch’s membrane.1 A few cases of CNVM lead to compromised metabolism and hypoxia

developing at the edge of a demarcation line of the outer retinal layers due to elevation of http://bjo.bmj.com/ have been reported in both chronic rhegma- the retina from the .6 RPE cells may on September 24, 2021 by guest. Protected copyright.

Figure 1 (A) Colour fundus photograph showing pigment line, pigment epithelial Figure 2 Histopathology of excised choroidal neovascular membrane. (A) Photomicrograph showing hypertrophy, and bordering haemorrhage from a fibrovascular membrane lined on its posterior aspect by an incomplete row of RPE cells subfoveal extension of choroidal neovascular (haematoxylin and eosin ×80). Inset shows numerous macrophages staining for macrophage marker membrane. (B) Fundus fluorescein angiogram PGM1 (PGM1 immunostain ×80). (B) Focal neovascularisation of membrane core is demonstrated demonstrating the subfoveal neovascular by endothelial cells showing immunoreactivity for von Willebrand stain (von Willebrand immunostain membrane. (C) Postoperative colour fundus ×100). (C) Membrane showing focal immunostaining for VEGF (arrow) (VEGF immunostain photograph showing attached retina and no ×80). (D) A similar distribution for bFGF is shown (bFGF immunostain ×80). Inset shows clinically visible recurrence of the membrane. appropriate negative control with no specific staining.

www.bjophthalmol.com 930 Letters

secrete VEGF in response to this hypoxic Br J Ophthalmol: first published as 10.1136/bjo.84.8.928c on 1 August 2000. Downloaded from insult and also secondary to mechanical stress incurred at the edge of the demarcation line.89 VEGF may then stimulate the recruitment and activation of monocytes, which in turn could promote mediators of angiogenesis.10 It is therefore possible that the liberation of neo- vascular growth factors in this setting may have contributed further to the development of CNVM in our patient.

RHY Asaria is supported by the June Sutor Fellow- ship. DNPARMAR Moorfields Eye Hospital, London R H Y ASARIA Moorfields Eye Hospital and Institute of Ophthalmology, London P LUTHERT Institute of Ophthalmology D G CHARTERIS Moorfields Eye Hospital and Institute of Ophthalmology Correspondence to: Mr D G Charteris, Vitreoretinal Unit, Moorfields Eye Hospital, City Road, London ECIV 2PD Accepted for publication 16 March 2000

1 Green WR, Wilson DJ. Choroidal neovasculari- sation. Ophthalmology 1986;93:1169–76. 2 Gass JDM. Stereoscopic atlas of macular diseases. 3rd ed. St. Louis: Mosby, 1987:716. 3 Lopez PF, Aaberg TM, Lambert HM, et al. Choroidal neovascularisation occurring within a demarcation line. Am J Ophthalmol 1992; 114:101–2. 4 Benson WE, Nantawan P, Morse PH. Character- istics and prognosis of retinal detachments with demarcation line. Am J Ophthalmol 1977;84: 641–4. 5 Grossniklaus HE, Gass JD.Clinicopathologic correlations of surgically excised type 1 and type 2 submacular choroidal neovascular mem- branes. Am J Ophthalmol 1998;126:59–69. 6 Prost M. Experimental studies on the angiogenic activity of the detached retina. Graefes Arch Clin Exp Ophthalmol 1990;228:83–5. 7 Bonnet M. Peripheral neovascularisation compli- cating rhegmatogenous retinal detachment of

long duration. Graefes Arch Clin Exp Ophthalmol http://bjo.bmj.com/ 1987;225:59–62. 8 Aiello LP, Northrup JM, Keyt BA, et al. Hypoxic regulation of vascular endothelial growth factor in retinal cells. Arch Ophthalmol 1995; 113: 1538–44. 9 Seko Y, Seko Y, Fujikura H, et al. Induction of vascular endothelial growth factor after applica- tion of mechanical stress to retinal pigment epi- thelium of the rat in vitro. Invest Ophthalmol Vis Sci 1999;40:3287–91.

10 Oh H, Takagi H, Takagi C, et al. The potential on September 24, 2021 by guest. Protected copyright. angiogenic role of macrophages in the formation of choroidal neovascular membranes. Invest Ophthalmol Vis Sci 1999;40:1891–8.

Simultaneous metastases of cutaneous malignant melanoma to and choroid Figure 1 Fundus photograph of the right (A) and the left (B) eye, respectively, showing extensive EDITOR,—We report an unusual case of a metastatic deposits in the choroid. cutaneous malignant melanoma which metas- infiltrate seen at the edges. It had been excised mm in size on the lateral aspect of the bulbar tasised to the conjunctiva in one eye and the completely with no vascular or lymphatic conjunctiva. Left eye anterior segment exam- choroid in both eyes nearly 2 years after the invasion seen in the section. He had been ination was normal. The intraocular pressure initial presentation. thoroughly screened and a computed tomo- was 17 mm Hg in both the eyes. Fundus graph (CT) scan of the abdomen and head examination of both the eyes revealed multi- CASE REPORT had not revealed any metastases. Subse- ple, widespread, irregular subretinal pig- A 42 year old white man presented with a his- quently, he had been followed up on a 4 mented deposits (Fig 1), some flat and some tory of a small superficial black mark in the monthly basis over the next 2 years and no slightly elevated. There was no associated temporal aspect of the right eye, which had recurrences had been found. During this cataract or retinal detachment. His creatinine increased in size for the past 2 months. There period he developed a severe form of asthma levels were found to be raised at 253 µmol/l, was no significant ocular history. Two years which was controlled by oral prednisolone 25 urea at 14.5 mmol/l, and lactate dehydroge- earlier he had had a large malignant mg per day. He otherwise felt well and on nase at 443 IU/l. Urine examination showed melanoma, 4.5 × 3.5 cm, removed from his examination seemed to be in good general both blood and protein present. lower back. On histopathology, this had been health. An enlarged lymph node was found in A diagnosis of cutaneous malignant diagnosed as a superficial spreading type his left axilla. Visual acuity was 6/6 in the right melanoma with simultaneous metastases to (Clarke’s level IV with Breslow thickness of eye and 6/5 in the left eye. Examination of the the conjunctiva and choroid and possible 3.5 mm). The mitotic count was 5 per 10 high anterior segment in the right eye revealed a widespread metastases was made. The patient power field (HPF) with a sparse lymphocytic small superficial blackish brown mark about 3 was counselled and referred to the oncologist

www.bjophthalmol.com Letters 931

present with pain and redness due to second- 5 De Bustros S, Augsberger JJ, Shields JA, et al. Br J Ophthalmol: first published as 10.1136/bjo.84.8.928c on 1 August 2000. Downloaded from ary caused by infiltration of the Intraocular metastases from cutaneous malig- nant melanoma. Arch Ophthalmol 1985;103: trabecular meshwork or angle closure due to 937–40. an annular haemorrhagic choroidal 6 Letson A, Davidorf F. Bilateral retinal metastases detachment.5 Retinal deposits are very rare from cutaneous malignant melanoma. Arch and may cause blurred vision.6 DiVerentiation Ophthalmol 1982;100:605–7. 7 Bell RWD, Ironside JW, Fleck BW, et al. Cutane- between secondary melanomas in the choroid ous malignant melanoma metastatic to the and a primary melanoma is important in order choroid: a clinicopathological case report. Eye to decide on the type of management. 1995;9:650–3. Bilateral diVuse uveal melanocytic prolifera- 8 Shields CL, Shields JA, Gross NE, et al.Survey of 520 eyes with uveal metastases. Ophthalmology tion is an important diVerential diagnosis in 1997;104:1265–76. our patient but he had no associated cataract, 9 Clark WH, From L, Bernardino EA, et al. The retinal detachment, or severe visual impair- histogenesis and biological behavior of primary ment. The time interval between the initial human malignant melanomas of the skin. 1969;29:705–27. presentation of the skin lesion and the occur- Cancer Res rence of metastases may vary from months up to 10 years.37 The occurrence of ocular Acute in metastases usually indicates grave prognosis treatment of xerophthalmia owing to widespread visceral disease, as was the case in our patient. He had undergone EDITOR,—Vitamin A deficiency remains a regular thorough screening for 2 years but no leading cause of blindness worldwide with signs of metastases were found during this xerophthalmia aVecting 5–10 million chil- period. The first external sign of secondary dren, resulting in 250 000–500 000 new cases disease was the presence of the conjunctival of blindness each year. In the developed Figure 2 (A) Histopathological section of the lesion, which led to the discovery of the world, vitamin A deficiency is rare and usually conjunctival lesion (haematoxylin and eosin intraocular lesions and the axillary node × occurs in the setting of malabsorptive states stain; original magnification 10 ) showing the involvement. Metastases to the conjunctiva (such as cystic fibrosis and small bowel metastatic cells covered by the normal from a cutaneous malignant melanoma is disease), liver disease, or malnutrition. conjunctival epithelium. (B) Higher again very rare (less than 1%) and is usually magnification of the same area (original Xerophthalmia is a medical emergency × associated with secondaries elsewhere in the carrying a high risk of blindness, infection and magnification 40 ) showing melanin pigment 8 granule laden cells. eye. These need to be diVerentiated from death. Immediate administration of massive other conditions such as primary acquired doses of vitamin A is required. Such rapid res- for possible chemotherapy. Surgery with a melanosis, naevus, adrenochrome deposits, toration of vitamin status is felt to be wide excision of the conjunctival lesion was direct extensions from melano- extremely safe at recommended doses. Appro- performed the next day and the tissue was sent mas, and foreign body granulomas. The mode priate dosing regimens in infants have been for histopathological examination. It was of treatment of metastatic cutaneous malig- less clear than in older children and adults.1 reported as consisting of a dense cellular infil- nant melanoma in the eye can range from Reports of side eVects are limited, and trate in the subepithelial tissue, with atypical local excision as in small localised therefore we report a case of acute sixth nerve melanocytes without any melanocytic activity tumours, and enucleation for a painful blind palsy in an infant receiving intramuscular in the overlying surface epithelium. The tissue eye or palliative treatment comprising chemo- vitamin A for xerophthalmia secondary to showed a positive staining for S100 protein therapy and radiotherapy if the disease is cystic fibrosis. 1 and HMB45 antibody, both of which are spe- widespread, as is often the case. Patients with cific for malignant melanoma. There was no a single choroidal metastasis may be consid- ered for radioactive plaque treatment.7 Previ- CASE REPORT pre-existing naevus and this was compatible A 5 month old male infant with a long history with a metastatic malignant melanoma (Fig ous studies have reported a median survival rate of 72 days with a maximum survival of of feeding intolerance was admitted to our http://bjo.bmj.com/ 2). hospital for severe irritability and failure to CT scans of the abdomen and the head 183 days and less than 10% survive up to 8 months after the onset of ocular symptoms.2 thrive. In the course of his examination, a revealed no metastatic disease. Within a week sweat test was performed confirming the diag- he developed abdominal pain and headache Although the survival rates are partly related 9 nosis of cystic fibrosis. Appropriate nutritional with vomiting which was relieved by dexa- to the depth of the dermal invasion ocular metastases with only superficial spreading therapy and pancreatic enzyme replacement methasone and was thought to be due to was commenced. meningeal metastases. Chemotherapy was type of melanomas have been reported and this was also true of our patient. Within days The infant had also been treated by his pae- instituted with weekly intravenous vindesine 4 diatrician for “” of his right eye 2 of being diagnosed as having ocular metas- mg/m and tamoxifen 160 mg orally. Four on September 24, 2021 by guest. Protected copyright. tases, he developed signs of widespread for the preceding 2 months with topical days later he developed severe nose bleeds antibiotics. On the ophthalmic examination, with clots. His platelet count at that point was secondaries, which led to his death within weeks. the infant’s visual acuity was fix and follow normal and he was thought to have metastases bilaterally. Extraocular motility was full and in the postnasal space. His condition deterio- SUSHMA DHAR-MUNSHI the eyes were orthophoric. Anterior segment rated rapidly with development of right sided Department of Ophthalmology, East Surrey Hospital, examination revealed conjunctival xerosis of pleuritic chest pain and haemoptysis and he Redhill, Surrey, RH1 5RH both eyes, and an inferior of the died 3 weeks later. M AMEEN right eye measuring 2×4 mm. Fundus exam- Department of Histopathology ination was normal in both eyes. A diagnosis COMMENT ROGER S WILSON of xerophthalmia was made. Secondary metastatic disease in the eye is rare Department of Ophthalmology Vitamin A therapy was promptly com- compared with other sites in the body and Correspondence to: Ms Sushma Dhar-Munshi, menced, with 50 000 IU (water miscible reti- simultaneous secondaries in both anterior and Department of Ophthalmology, Room no 5.012, nyl palmitate) intramuscularly to be given posterior segment are highly unusual.1 The Level 5, Lanesborough Wing, St George’s Hospital, immediately and then to be repeated on the incidence of histopathologically demonstrable Blackshaw Road, London SW17 0QT following day. After the first 50 000 IU, cutaneous malignant melanoma metastasising Accepted for publication 16 March 2000 prominent bulging of the fontanelle was to these sites was seen in five of 15 cases observed, although the infant remained alert (33%) with disseminated cutaneous malig- 1 Volpe NJ, Albert DM : Metastases to the . and happy, and was feeding well. The second nant melanoma in an necropsy series and is In: Albert DM, Jakobiec FA. Principles and prac- dose of 50 000 IU was therefore postponed 2 tice of ophthalmology. Philadelphia: WB Saun- thought to be more common in men. The ders, 1994;chapter 266:3260–70. for 48 hours, to be administered in two presentation in the eye has been variously 2 Fishman ML, Tomaszewski MM, Kuwabara T. divided doses over 2 consecutive days. These described as ranging from distinct tumours in Malignant melanoma metastatic to the eye. Arch doses were well tolerated, with gradual the fundus or small diVuse infiltrates, anterior Ophthalmol 1976;94:1309–11. improvement of the bulging fontanelle over a 3 Char DH, Schwartz A, Miller TR, et al. Ocular refractory to treatment, iris heterochro- metastases from systemic melanoma. Am J week. Five days after the initial vitamin A mia, brownish coloured due to Ophthalmol 1980;90:702–7. dose, a complete abduction deficit of the tumour cells, diVuse pigmentation of the iris 4 Bowman CB, Guber D, Brown CH, et al. infant’s left eye was noted, in keeping with an Cutaneous malignant melanoma with diVuse and the lens, aqueous and vitreous seedlings, intraocular metastases. Arch Ophthalmol 1994; acute sixth nerve palsy of the left eye. The and conjunctival pigmentation.34Patients can 112:1213–16. infant still remained alert and happy, and

www.bjophthalmol.com 932 Letters

there were no other signs of raised intracranial 6 Becker NH, Sutton CH. Pathologic features of the Br J Ophthalmol: first published as 10.1136/bjo.84.8.928c on 1 August 2000. Downloaded from pressure. The corneal ulcer of the right eye choroid plexus. I. Cytochemical eVects of hyper- vitaminosis A. Am J Pathol 1963;43:1017–30. was fully healed at this time. The infant was 7 Sommer A, Muhilal, Tarwotjo I, et al. Oral versus followed for 2 months over which time the intramuscular vitamin A in the treatment of sixth nerve palsy fully resolved. There were no xerophthalmia. Lancet 1980;1:557–9. other neurological sequelae. The infant con- tinued to receive oral vitamin A supplementa- Successful treatment of ocular invasive tion after discharge. mould infection (fusariosis) with the new antifungal agent voriconazole COMMENT Prompt mega-dose administration of vitamin EDITOR,—Voriconazole is a new, highly po- A is essential in the management of xeroph- tent, triazole with broad spectrum activity thalmia. Oral administration is preferred against fungi, including moulds as well as flu- because of its safety, cost, and eVectiveness. conazole resistant Candida spp.1 Like other Figure 2 Ultrasound biomicroscopy discloses The recommended regimen is 200 000 IU of azole antifungal agents it interferes with relapse of intraocular fungal disease. vitamin A on the day of diagnosis, the next ergosterole biosynthesis. Its antifungal activity day, and 4 weeks later. In the rare instances in has been shown in several experimental as well systemic itraconazole (Sempera) 200 mg which children are unable to swallow or as clinical studies.2–5 absorb oral vitamin A, intramuscular injection twice daily (a triazole which is known to be of water miscible retinyl palmitate 55 mg eVective against some amphotericin B resist- CASE REPORT (100 000 IU) should be substituted—given ant mould species) for 3 days again with no immediately, the next day, and 4 weeks later. In November 1998, a 16 year old girl was clinical eVect. Children 6–11 months of age should receive transferred to the university eye hospital in Owing to the lack of response to conven- half these doses and children less than 6 Duesseldorf with a severe ulcerative hypopyon tional therapy, we obtained the new antifungal in the left eye, from which she had months of age one quarter of these doses.2 In agent voriconazole, from Pfizer, on an com- been su ering for 3 months after swimming in our patient, because the child’s age was V passionate use basis. Voriconazole was started a lake in Italy. Smears, scrapings, and serology approaching 6 months, we chose to administer at a dosage of 6 mg/kg intravenously twice on gave no hint of the aetiology. Despite intensive 50 000 IU doses. day 1 followed by 4 mg/kg intravenously twice topical antibacterial, anti-acanthamoebal, Acute vitamin A toxicity generally occurs in daily. This well tolerated therapy produced a antifungal, and antiherpetic therapy, as well as children when a single dose greater than significant clinical improvement. However, cryoapplication, her clinical situation had 330 000 IU is ingested, although some infants after 10 days the disease relapsed (Fig 2). deteriorated continuously before admission to can be adversely aVected by single doses as Owing to the initial positive response it was our hospital. As an optical rehabilitation was low as 100 000 IU.34Typical features include considered that the relapse might be due to unlikely, owing to the severely infiltrated a bulging fontanelle in infants, raised cerebro- suboptimal penetration to the site of infection. , a perforating keratoplasty was per- spinal fluid (CSF) pressure, nausea and vom- Voriconazole therapy was changed to 6 mg/kg formed. Postoperatively, the patient was given iting, vertigo, and blurred vision or . by mouth twice daily. Voriconazole was also systemic as well as topical antibiotics. The first These side eVects are generally transient and injected intracamerally, at a dosage of 3 days postoperatively were inconspicuous, subside within 1–2 days. Chronic ingestion of 10 µg/0.1 ml. Topical antifungal therapy was but from the sixth day on a hypopyon could large amounts of vitamin A can result in pseu- switched from amphotericin B 0.3% every again be seen. The hypopyon progressed and dotumour cerebri. hour to voriconazole 1% every half hour. In we could identify, by ultrasound biomicros- This case demonstrates acute toxicity oc- addition, any remaining suspicious intraocular copy the focus at the remaining recipient cor- curring after a cumulative dose of 100 000 IU material was again excised and the anterior nea. We removed this focus which was highly given over 4 days. The sixth nerve palsy chamber was irrigated with a 3 µg/ml vorico- suspected of being a fungal colony and sent it occurred presumably from raised CSF pres- nazole solution. After this procedure, healing to the microbiology department (an attempt sure, a phenomenon that is not fully under- finally took place, and the patient was released to culture bacteria or fungi failed). Antifungal http://bjo.bmj.com/ stood but may be due to altered CSF from hospital; voriconazole was discontinued therapy with systemic fluconazole (200 mg/ resorption or production.56 Acute toxicity after 8 weeks. The corneal graft remained day intravenously) and topical amphotericin B from intramuscular vitamin A (particularly clear and best corrected vision was 0.9. There (0.3% every hour) were started, but the clini- water miscible forms) may be more likely were no local or systemic adverse eVects dur- cal picture still deteriorated. At that time a because of the higher serum levels that are ing this highly potent therapeutic regimen. A filamentous fungus was diagnosed histopatho- achieved more rapidly compared with oral transient elevation of liver enzymes (a known logically in the excised corneal button (Fig 1). preparations.7 Nevertheless, this case attests to adverse event of azole antimycotic agents) at Because of the morphological similarities the relative safety of vitamin A administration the end of therapy and after cessation has been between Aspergillus, Fusarium, and Pseudalle- in infants. attributed to the study drug. Topical adminis- on September 24, 2021 by guest. Protected copyright. scheria boydii on histology these potent causes tration was well tolerated. EUGENE W M NG of keratitis could not be diVerentiated by this NATHAN G CONGDON technique alone. Immunohistochemical ex- ALFRED SOMMER amination of mycelia containing tissue sec- COMMENT Wilmer Ophthalmological Institute and the Dana Center tions with a panel of specific antifungal This is the first time that the eYcacy of for Preventive Ophthalmology, The Johns Hopkins antibodies, all Grocott methenamine silver voriconazole in the treatment of ocular Hospital, and the Johns Hopkins University School of invasive fungal infection has been demon- Hygiene and Public Health, Baltimore, MD, USA positive hyphae were identified as Fusarium species because a strong and uniform reactiv- strated. Topical administration has been toler- Correspondence to: Nathan G Congdon, MD, ated well even when injected into the anterior MPH, The Wilmer Ophthalmological Institute and ity was obtained only with a heterologously the Dana Center for Preventive Ophthalmology, The absorbed polyclonal antibody raised towards chamber. Its obvious antifungal activity and Johns Hopkins Hospital, 600 North Wolfe Street, somatic antigens of Fusarium solani.6 favourable pharmacological properties, espe- Baltimore, MD 21287, USA As the antifungal therapy had no eVect cially the low range of side eVects, will make this new drug attractive for future studies on Accepted for publication 15 March 2000 whatsoever, the regimen was changed to invasive ocular infections. ALEXANDER REIS 1 Agoestina T, Humphrey JH, Taylor GA, et al. RAINER SUNDMACHER Safety of one 52-µmol (50 000 IU) oral dose of Eye Hospital, Heinrich-Heine-University Duesseldorf vitamin A administered to neonates. Bull World Health Org 1994;72:859–68. KATHRIN TINTELNOT 2 Sommer A. Treatment. In: Vitamin A deficiency Robert-Koch-Institut Berlin and its consequences. A field guide to detection and control. Geneva: World Health Organisation, HANSJÜRGEN AGOSTINI 1994:36–40. Eye Hospital, University of Freiburg 3 Hathcock JN, Hattan DG, Jenkins MY, et al. Evaluation of vitamin A toxicity. Am J Clin Nutr HENRIK ELVANG JENSEN 1990;52:183–202. The Royal Veterinary and Agricultural University, 4 Marie J, See G. Acute hypervitaminosis A of the Department of Pharmacology and Pathobiology, infant. Am J Dis Child 1953;87:731–6. Copenhagen 5 Maddux GW, Foltz FM, Nelson SR. EVect of vitamin A intoxication on intracranial pressure Figure 1 Grocott methenamine silver positive CHRISTOPH ALTHAUS and brain water in rats. J Nutr 1974;104:478–82. hyphae in the excised corneal button. Eye Hospital, Heinrich-Heine-University Duesseldorf

www.bjophthalmol.com Letters 933

Correspondence to: Dr Alexander Reis, Eye Hospi- 200 20 000 Br J Ophthalmol: first published as 10.1136/bjo.84.8.928c on 1 August 2000. Downloaded from tal, Heinrich-Heine-University, Moorenstrasse 5, 40225 Duesseldorf, Germany /l)

[email protected] 6 Accepted for publication 13 April 2000 150 15 000 × 10

1 Sanati H, Belanger P, Fratti R, et al. Anew triazole, voriconazole (UK-109,496), blocks 100 10 000 sterol biosynthesis in Candida albicans and Candida krusei. Antimicrob Agents Chemother 1997;41:2492–6. 2 Nguyen HM, Yu CY. In vitro comparative eYcacy of voriconazole and traconazole against 50 5000 fluconazole-susceptible and resistant Crypto- coccus neoformans isolates. load ( ) (copies/ml) Viral

Antimicrob Agents CD4+ count ( ) (cells Chemother 1998;42:471–2. 3 Martin MV, Yates J, Hitchcock CA. Comparison of voriconazole (UK-109,496) and itraconazole 0 0 in prevention and treatment of Aspergillus 0 12 24 fumigatus endocarditis in guinea pigs. Anitmi- crob Agents Chemother 1997;41:13–16. 4 Murphy M, Bernard EM, Ishimaru T, et al. Activity of voriconazole (UK-109,496) against clinical isolates of Aspergillus species and its Feb 1998 eVectiveness in an experimental model of Dec 1996 April 1998 April 1996 invasive pulmonary aspergilosis. Antimicrob intraocular

Agents Chemotther 1997;41:696–8. inflammation 5 Ruhnke M, Schmidt-Westhausen A, Trautmann Onset of severe vitritis Feb 1997 M. In vitro activities of voriconazole (UK- Ritonavir added, Immune recovery

109,496) against fluconazole-susceptible and Change of HAART, -resistant Candida albicans isolates from oral cavities of patients with human immuno- Start of triple therapy, deficiency virus infection. Antimicrob Agents Chemother 1997;41:575–7. Months following initial cytomegalovirus 6 Jensen HE, Salonen J, Ekfors TO. The use of immunohistochemistry to improve sensitivity Figure 2 CD4+ lymphocyte count and viral load. and specificity in the diagnosis of systemic 6 mycoses in patients with haematological malig- CASE REPORT ×10 /l and his CD4+ count was 128 cells nancies. JPathol1997;181:100–5. 6 A 43 year old man, diagnosed as HIV positive ×10 /l (Fig 2). in 1984, was treated in January 1996 for bilat- Six weeks after changing HAART, he com- Severe intraocular inflammation after a eral CMVR that responded to systemic ganci- plained of blurred left vision. Visual acuity was 6/6 right, 6/9 left. There was a left vitritis with change of HAART clovir. In April 1996 he started saquinavir, stavu- a white retinal lesion along the inferotemporal EDITOR,—Patients with previous cytomegalo- dine, and lamivudine. A viral load was 18 000 vessels at the margin of inactive CMVR (Fig virus retinitis (CMVR) have been observed to copies ×106/l and CD4+ count 40 cells ×106/l. 3). A diagnosis of relapse of CMVR was made get vitritis, cystoid macular oedema (CMO), In December 1996 ritonavir was added. and he was treated with intravenous ganciclo- and epiretinal membranes after commencing In February 1997 he developed immune vir. HAART (highly active antiretroviral recovery vitritis in both eyes. Best corrected Two weeks later vision was counting fingers, therapy).1–3 It is postulated that this is due to visual acuities (BCVA) were 6/6, N5 right; 6/6, the vitritis was worse, and the retinal lesion the improved CD4+ function that occurs with N8 left. A viral load was now 7800 copies had extended with more haemorrhage. He HAART.4 ×106/l and CD4+ count 100 cells ×106/l. A was treated for presumed toxoplasmosis with http://bjo.bmj.com/ We present a patient with previously treated fluorescein angiogram showed bilateral CMO sulphadiazine, pyramethamine, and folinic CMVR and immune recovery vitritis who with macular ischaemia (Fig 1) and he was acid but 1 week later his vision was hand developed further severe intraocular inflam- treated with 250 mg sustained release oral movements and the lesion was larger (Fig 4). mation 6 weeks after changing HAART. acetazolamide, twice daily. After 1 month’s A diagnostic vitrectomy was performed. treatment there was a subjective improvement Polymerase chain reaction (PCR) was nega- in vision but no objective change in VA. In tive for CMV, toxoplasmosis, varicella zoster, September 1997 his BCVAs were 6/6, N5 and Epstein–Barr viruses. Cytology did not reveal lymphoma.

right; 6/6, N6 left. In December 1997 his on September 24, 2021 by guest. Protected copyright. CMVR was inactive and ganciclovir was One week later the eye was painful and stopped. vision was perception of light. A retinal biopsy In February 1998 he developed marked was performed in an area of active inflamma- lipodystrophy and consequently was changed tion. Histology showed retinal necrosis and to efavirenz, hydroxyurea, didanosine, and exudates. No viral inclusion bodies were continued on stavudine. By April 1998 his found and stains for acid fast bacilli, fungi, viral load had fallen to less than 500 copies and toxoplasma cysts were all negative. A few atypical lymphocytes were seen and PCR for

Figure 1 (A) Fluorescein angiogram of the Figure 3 Inferotemporal, white retinal lesion at Figure 4 One week later the lesion has right eye at 38 seconds demonstrating macular margin of mature CMVR with surrounding increased in size and extended to involve all ischaemia. (B) Macular oedema evident in a haemorrhage, sheathing of neighbouring veins retinal layers. Retinal vessels are obscured and late phase fluorescein angiogram of the left eye. but no obvious involvement of arterioles. haemorrhage persists.

www.bjophthalmol.com 934 Letters

B cell clonality showed oligoclonal banding. A report of oriental herbal medicine (kampo) Table 1 Composition of the herbal medicine Br J Ophthalmol: first published as 10.1136/bjo.84.8.928c on 1 August 2000. Downloaded from contrast enhanced magnetic resonance imag- induced keratopathy. (7.5 g of this product contains 5.7 g of dried ing of the brain and orbits was normal. extract obtained from mixed raw herbs in the above ratio) Eighteen months later the BCVAs are 6/6, CASE REPORT N5 right; perception of light, left. A chorioreti- A 30 year old Japanese woman was referred to nal scar persists in the macular and temporal JP Scutellaria root 2.0 g Juntendo University Hospital with the com- JP Glycyrrhiza root 2.0 g retina of the left eye but there is no active plaint of bilateral . Visual acuity JP Platycodon root 2.0 g inflammation in either eye. was 20/20 in both eyes. Slit lamp examination JP Gypsum 2.0 g disclosed dust-like opacities in the epithelial JP Atractylodes rhizome 2.0 g JP Rhubarb rhizome 1.5 g COMMENT layer in both central , and brown JP Schizonepeta spike 1.2 g Investigations in this patient failed to identify coloured precipitates, which spread radially JP Gardenia fruit 1.2 g any cause for the intraocular inflammation; from the central cornea (Fig 1A). No corneal JP Peony root 1.2 g however, the cessation of the inflammatory staining was observed with fluorescein. No JP Cnidium rhizome 1.2 g process in the absence of any specific treat- other ocular abnormality was found. There JP Japanese angelica root 1.2 g ment is similar to the clinical course of were no remarkable findings in her past or JP Mentha herb 1.2 g JP Saposhnikovia root 1.2 g immune recovery vitritis and suggests a family history. JP Ephedra herb 1.2 g non-infectious mechanism. The temporal as- The patient underwent therapeutic and JP Forsythia fruit 1.2 g sociation with the change in HAART, together diagnostic superficial keratectomy that pro- JP Ginger rhizome 0.4 g with the PCR findings, both imply an vided epithelial layer for ultrastructural study. Talc 3.0 g immunological cause. It is unclear why this The corneal epithelial layer was processed for Anhydrous mirabilitum 0.75 g response was uniocular. routine electron microscopy. Electron micro- The presence of multiple discrete bands on scopic examination disclosed corneal epithe- was observed until now, 4 years after the first PCR may indicate a premalignant lymphopro- lial cells with numerous lamellar inclusion examination. liferation but 18 months later the eye is quiet bodies formed by series of concentrically with no recurrence and the patient remains arranged lamellae suggestive of lipid-like well. Our hypothesis is that the intraocular material (Fig 1B). COMMENT inflammation occurred because the new com- The patient was submitted to laboratory Although oriental herb medicines have been bination HAART produced a second, very tests in order to investigate a possible meta- beneficial to patients, scientific explanation of exaggerated immune response to pre-existing bolic disease. No abnormal data were detected their pharmacological mechanisms has lagged antigens. except for slightly high level of total blood behind the widespread use of kampo in Clinicians should be aware that changing cholesterol. Concerning the drug history, the clinical practice.1 In this case, the clinical and the combination of HAART may be associ- patient informed us that she had been taking morphological findings were similar to those 2 ated with aggressive intraocular inflammation an oral oriental herbal medicine for chronic observed in Fabry’s disease and in drug 3–5 with an oligoclonal lymphocyte response. constipation for about 5 years. The composi- induced keratopathy. In drug induced lipid Early recognition and treatment with systemic tion of the drug is shown in Table 1. Two years storage keratopathy, the corneal deposits are steroids may have prevented blindness in our before the present complaint, the patient had bilateral, dose and duration related, and patient. the same symptom of photophobia which gradually disappear after the drug is withdrawn.6 Although kampo is believed to be TIMOTHY L JACKSON gradually disappeared several months after WILLIAM MEACOCK withdrawal of the herbal medicine. One very safe, it seems advisable to dictate caution Medical Eye Unit, St Thomas’s Hospital, month before the present complaint, she with respect to this possible adverse eVects. London SE1 7EH started taking the herbal medicine for consti- TORU AKATSU MIKE YOULE pation. The patient was advised to withdraw RUTH M SANTO Kobler Centre, Chelsea and Westminster Hospital, the herbal medicine. Three months after with- KIYOO NAKAYASU London drawal, the corneal opacities decreased and ATSUSHI KANAI Department of Ophthalmology, Juntendo University the patient noticed relief of symptoms. One http://bjo.bmj.com/ ELIZABETH M GRAHAM School of Medicine Medical Eye Unit, St Thomas’s Hospital, year after withdrawal, the corneal lesions had Correspondence to: Kiyoo Nakayasu, MD, Depart- London SE1 7EH disappeared completely. No sign of recurrence ment of Ophthalmology, Juntendo University School Correspondence to: Dr E M Graham of Medicine, 3-1-3, Hongo, Bunkyo-ku, Tokyo, 113- [email protected] 8431, Japan Accepted for publication 13 April 2000 Accepted for publication 13 April 2000

1 Karavellas MP, Lowder CY, MacDonald C, et al. 1 Baker S, Thomas PS. Herbal medicine precipi-

Immune recovery vitritis associated with inac- tating massive haemolysis. Lancet 1987;i:1039– on September 24, 2021 by guest. Protected copyright. tive cytomegalovirus retinitis: a new syndrome. 40. Arch Ophthalmol 1998;116:169–75. 2 Frost P, Tanaka Y, Spaech GL. Fabry’s disease: 2 Silverstein BE, Smith JH, Sykes SO, et al.Cystoid glycolipid lipidosis. Histochemical and electron- associated with cytomegalovirus microscopic studies of two cases. Am J Med retinitis in patients with the acquired immuno- 1966;40:618–27. deficiency syndrome. Am J Ophthalmol 1998; 3 Weiss JN, Weinberg RS, Regelson W. Keratopa- 125:411–5. thy after oral administration of tilorone hydro- chloride. 1980; :46–53. 3 Zegans ME, Walton RC, Holland GN, et al. Am J Ophthalmol 89 Transient vitreous inflammatory reactions asso- 4 D’Amico DJ, Kenyon KR, Ruskin JN. Amiodar- ciated with combination antiretroviral therapy one keratopathy. Arch Ophthalmol 1981;99:257– in patients with AIDS and cytomegalovirus 61. retinitis. 1998;125:292–300. 5 Holland EJ, Stein CA Palestine AG, et al. Am J Ophthalmol Suramin keratopathy. 1988; 4 Autran B, Carcelain G, Li TS, et al. Positive Am J Ophthalmol eVects of combined antiretroviral therapy on 106:216–20. CD4+ T cell homeostasis and function in 6 Freddo TF, Waring GO. Pathologic responses in the cornea. In: Leibowithz HM, Waring GO, advanced HIV disease. Science 1997;277:112–6. eds. Corneal disorders. Clinical diagnosis and man- agement. 2nd ed. Philadelphia: Saunders, 1998: 154–200. Oriental herbal medicine induced epithelial keratopathy Branch retinal artery occlusion; another EDITOR,—“Kampo” is the name given to an of sildenafil oriental herb medicine which has been used in China and Japan for more than 2000 years. EDITOR,— Sildenafil is the oral treatment Kampo is believed to be very mild and a safe for erectile dysfunction and was licensed medicine and so far there has been no report Figure 1 (A) Slit lamp examination shows throughout Europe in September 1998. It is a of kampo induced keratopathy. numerous dust-like opacities in the epithelium at potent, selective inhibiter of the isoenzyme central cornea and brown coloured precipitates We report a case of epithelial keratopathy, spreading radially from central cornea in both eyes. phosphodiesterase type 5 (PDE 5). Inhibition which occurred in a patient who had taken (B) Numerous membranous lamellar inclusion of PDE5 leads to prolongation of cyclic oral oriental herbal medicine for 5 years. To bodies in the corneal epithelial cells, suggestive of guanosine monophosphate (cGMP) activity the best of our knowledge, this is the first lipid-like material (×16 000). in erectile tissue and increases the natural

www.bjophthalmol.com Letters 935

vasodilatory actions of nitric oxide on the cav- COMMENT report clearly suggests that the earlier claim Br J Ophthalmol: first published as 10.1136/bjo.84.8.928c on 1 August 2000. Downloaded from ernosal smooth muscle, facilitating the erectile A number of adverse eVects of sildenafil have that there is no cause for alarm over retinal response in men with erectile dysfunction.1 been reported and these include headache, side eVects of sildenafil8 must be re-examined Whereas many ocular adverse eVect of silde- facial flushing, dyspepsia, and nasal conges- and a potentially blinding complication like 2–5 nafil have been reported, we present, to the tion. There have been reports of prolonged the one reported here should be seriously best of our knowledge, the first case report of erection and priapism, myocardial infarction,6 considered and discussed with all the patients branch central retinal artery occlusion follow- sudden cardiac arrest, ventricular arrhyth- started on sildenafil, more so because of the ing the use of sildenafil. 2 mias, and hypertension. In patients taking fact that most of the patients using this medi- organic nitrates, it can lead to a sudden and cation are already at high risk of developing 2 CASE REPORT severe drop in blood pressure. A cardiac vascular accidents in the body. A 69 years old man presented with a sudden examination, including exercise treadmill painless loss of vision in the left eye 2 days testing has been recommended before start- AJAY TRIPATHI previously. The patient was fit and healthy ing patients on sildenafil.7 Various ocular side NIALL P O’DONNELL otherwise and had no history of glaucoma, eVects have been described following the use Southport Eye Unit, Pilkington Road, diabetes, hypertension, or other systemic of sildenafil. These fall into two major Southport PR8 6PH vascular diseases. Visual acuity was 6/6 in the categories: (i) those secondary to the weak Correspondence to: Mr Ajay Tripathi right eye and 6/24 in the left eye. Anterior seg- inhibitory eVects of sildenafil on the isoen- [email protected] ment examination was normal apart from a zyme PDE6 in the retina.3 These side eVects Accepted for publication 18 April 2000 mild relative left aVerent pupillary defect. include temporary loss of vision, increased Fundus examination of right eye was normal intraocular pressure, green/blue tinging of whereas fundus examination of the left eye vision, increased sensitivity to light, and 1 Umrani DN, Goyal RK. Pharmacology of 2 sildenafil citrate. Indian J Physiol Pharmacol revealed a superotemporal branch retinal blurred vision. There have also been reports 1999;43:160–4. artery occlusion. As the patient did not have of retinal degeneration. A decrease in the 2 Marmor MF, Kessler R. Sildenafil (Viagra) and any of the risk factors predisposing to arterial a-wave and b-wave amplitude in the elec- ophthalmology. Surv Ophthalmol 1999;44:153– occlusion a more detailed history was sought troretinogram (ERG) of five healthy men 1 62. and the patient informed us that he had taken hour after oral intake of 100 mg sildenafil has 3 Gonzalez CM, Bervig T, Huang CF, et al. a dose of Viagra (100 mg) a few hours before also been reported and these changes com- Sildenafil causes a dose and time dependent 5 downregulation of phosphodiesterase type 6 he experienced loss of vision in left eye. pletely disappeared 5 hours later. (ii) Ocular expression in the rat retina. Int J Impot Res Cardiac examination revealed sinus rhythm, vascular events such as haemorrhages, venous 1999;11(Suppl 1):S9–14. normal heart sounds, and there was no carotid occlusion, and anterior ischaemic optic neu- 4 Donahue SP, Taylor RJ. -sparing third bruit or thrill. Immediate measures taken to ropathy have been mentioned2 but so far there nerve palsy associated with sildenafil citrate restore the circulation (intravenous Diamox, has been no referenced report of retinal artery (Viagra). Am J Ophthalmol 1998;126:476–7. 5 Vobig MA, Klotz T, Staak M, et al. Retinal side- ocular massage, rebreathing into a bag, etc) occlusion following the use of sildenafil. In eVects of sildenafil. Lancet 1999;353:375. proved futile and vision remained 6/24 over a addition to these ocular side eVects, a pupil 6 Porter A, Mager A, Birnbaum Y, et al. Acute 3 months follow up period. Full blood counts, sparing third nerve palsy due to sildenafil has myocardial infarction following sildenafil citrate serum electrolytes, fasting blood glucose also been reported.4 In the case reported (Viagra) intake in a nitrate-free patient. Clin levels, fasting total lipids and cholesterol, here, a sudden rise in intraocular pressure or Cardiol 1999;22:762–3. 7 Kloner RA. Viagra: what every physician should erythrocyte sedimentation rate, and plasma an embolic phenomenon due to short lived know. Ear Nose Throat J 1998;77:783–6. viscosity were normal. The patient has not cardiac arrhythmias may have produced 8 Zrenner E. No cause for alarm over retinal side- used sildenafil since then. branch retinal artery occlusion. This case eVects of sildenafil. Lancet 1999;353:340–1. http://bjo.bmj.com/ on September 24, 2021 by guest. Protected copyright.

www.bjophthalmol.com