Xanthomonas Maltophilia Endophthalmitis After Cataract

CASE REPORTS AND SMALL CASE SERIES

Report of Cases. Case 1. An 80- later, X maltophilia was isolated from year-old woman was evaluated for in- the culture that was resistant to cefta- Xanthomonas maltophilia creasing pain and decreased vision in zidime but sensitive to amikacin sul- Endophthalmitis After the left eye, 2 weeks after unevent- fate (Table 2). However, her clini- Cataract Surgery ful clear-corneal phacoemulsifica- cal condition continued to improve, tion and posterior chamber intraocu- with resolution of the hypopyon; vi- lar lens (IOL) insertion. Her medical sual acuity returned to 20/50 OS. A Xanthomonas maltophilia, previ- history was unremarkable. Visual small amount of retained lens cor- ously known as Pseudomonas malto- acuity in the affected eye was hand tex was noted at the 6-o’clock posi- philia and Stenotrophomonas malto- movements. Clinical findings in- tion. Gradual tapering of topical philia, is a gram-negative motile cluded a 5% hypopyon and marked medications was begun. bacillus that can be isolated from hu- vitritis. Vitreous tap was performed Three weeks after the initial man, animal, and environmental through the pars plana, and the pa- treatment, she returned with visual sources.1 It may cause potentially life- tient was given intravitreal injec- acuity in the left eye of light percep- threatening opportunistic systemic tions of ceftazidime, 2.25 mg; van- tion and recurrent hypopyon. Vitre- infections.1,2 Most isolates demon- comycin hydrochloride, 1.0 mg; and ous tap was performed and intravit- strate multidrug resistance, making dexamethasone sodium phosphate, real injections of amikacin sulfate, 0.4 it a highly virulent organism. Post- 0.4 mg. On the first day after the ini- mg, and dexamethasone sodium operative endophthalmitis caused by tial treatment, a combined regimen phosphate, 0.4 mg, were given. Cul- X maltophilia is rare. To date, only 2 was started with topical fortified cefta- tures of the vitreous aspirate were case reports have been published.3,4 zidime, vancomycin, and 1% pred- again positive for X maltophilia. Dur- We describe 4 additional patients nisolone acetate, every hour, and 1% ing the next 48 hours, she devel- with postoperative X maltophilia en- atropine sulfate, 3 times daily. No sys- oped worsening intraocular inflam- dophthalmitis treated between Janu- temic antibiotic therapy was used. mation; the visual acuity remained ary 1, 1996, and March 31, 1999, at Gram stain of the vitreous aspirate re- light perception. Pars plana vitrec- the Bascom Palmer Eye Institute, Mi- vealed many neutrophils, but no or- tomy was performed and intravit- ami, Fla (Table 1). ganisms were identified. Three days real injections of amikacin sulfate, 0.4

Table 1. Treatment Outcomes of Xanthomonas maltophilia Endophthalmitis*

Visual Acuity Time to Initial Intravitreal Initial Time to Subsequent Treatment Patient No. Surgery Infection, d Treatment (Dosage) PPV Recurrence, d (Dosage) Initial Final 1 PE and PCIOL 14 Vancomycin hydrochloride − 21 Intravitreal injection of amikacin HM 20/50 (1.0 mg), ceftazidime sulfate (0.4 mg), followed by (2.25 mg), and PPV, and repeat intravitreal dexamethasone sodium injection of amikacin sulfate phosphate (0.4 mg) (0.4 mg) 2 PE and PCIOL 26 Vancomycin hydrochloride − None None HM 20/30 (1.0 mg), ceftazidime (2.25 mg), and dexamethasone sodium phosphate (0.4 mg) 3 ECCE and PCIOL 6 Amikacin sulfate and − 45 PPV and intravitreal injection of 20/200 20/30 cefazolin sodium† vancomycin hydrochloride (1.0 mg) and ceftazidime (2.25 mg) 4 ECCE and PCIOL 5 Vancomycin hydrochloride + 7 Intravitreal injection of LP 20/400 (1.0 mg), ceftazidime ceftazidime (2.25 mg) ϫ2 and (2.25 mg), and subsequent PPV for dexamethasone sodium nonclearing vitreous opacities phosphate (0.4 mg)

*PPV indicates pars plana vitrectomy; PE, phacoemulsification; PCIOL, posterior chamber intraocular lens implant; minus sign, no initial PPV was performed; HM, hand movements; ECCE, extracapsular cataract extraction; plus sign, an initial PPV was performed; and LP, light perception. †Dosages not known.

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©2000 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 mg,anddexamethasonesodiumphos- sistent anterior chamber reaction Palmer Eye Institute for further phate,0.4mg,wereadministered.Dur- (2+) with retained lens cortex at the management of his condition. ing the vitrectomy, the silicone plate 5-o’clock position and was given a Best-corrected visual acuity was posterior chamber IOL dislocated into sub-Tenon injection of dexametha- 20/200 OS. The cornea was slightly the vitreous cavity but was positioned sone sodium phosphate, 40 mg, by edematous, with anterior chamber into the anterior chamber with a plan her ophthalmologist. Two days later, cells (2+ to 3+) but no hypopyon. The to exchange the IOL at a later date. At the visual acuity in the left eye de- posterior chamber IOL was in the bag the 9-month follow-up visit, visual creased to hand movements. Clini- with fluffy white cortical material for acuity was 20/50 OS and the vitritis cal findings included a 5% hypo- about 3 clock-hours. Dilated fun- resolved (Figure). pyon, vitritis, and no view of the dus examination revealed vitritis (2+) Case 2. A 70-year-old woman retina. A vitreous aspirate was per- with optic disc hyperemia and cys- was referred with increasing pain and formed, and she was given intravit- toid macular edema. The patient un- redness in her left eye. One month real injections of ceftazidime, 2.25 derwent an uncomplicated pars plana earlier, she underwent phacoemul- mg; vancomycin hydrochloride, 1.0 vitrectomy, partial capsulectomy, and sification and insertion of a poste- mg; and dexamethasone sodium received intravitreal injections of rior chamber IOL. Her early postop- phosphate, 0.4 mg. Cultures of the ceftazidime, 2.25 mg, and vancomy- erative course was uneventful, and vitreous aspirates were positive for X cin hydrochloride, 1.0 mg. Several she recovered 20/25 OS visual acu- maltophilia that was resistant to cefta- days later, X maltophilia was iso- ity by week 2. However, she had per- zidime but sensitive to amikacin lated from the culture of vitreous as- (Table 2). However, the patient had pirates that was sensitive to ceftazi- an excellent response to intravitreal dime but resistant to amikacin (Table Table 2. In Vitro Antibiotic ceftazidime treatment and 3 months 2). The vitritis resolved; visual acu- Sensitivities of Xanthomonas later, best-corrected visual acuity was ity improved to 20/30 OS at the maltophilia in Our Study* 20/30 OS and the vitritis resolved. 8-month follow-up visit. Case 3. A 46-year-old man Case 4. A 48-year-old man un- Patient No. developed pain and irritation 5 derwent an uneventful extracapsu- days after undergoing extracapsular lar cataract extraction with insertion Antibiotic 1 234 cataract extraction and posterior of posterior chamber IOL in his right Ceftazidime R R S S chamber IOL implantation in his eye in Nicaragua. Because of the Amikacin S S R R Gentamicin R R R R left eye. In Venezuela, he was diag- marked intraocular inflammation on Tobramycin S S R R nosed as having postoperative the fifth postoperative day, a clinical Ciprofloxacin S S R S endophthalmitis and was treated diagnosis of postoperative endoph- Imipenem R R R R with vitreous tap and intravitreal thalmitis was made and he was treated Polymyxin B S S S S injections of amikacin and cefazo- with subconjunctival gentamicin and Sulfamethoxazole- S SSR lin sodium. Vitreous cultures were topical tobramycin-prednisone drops trimethoprim reported to yield gram-negative every hour. Seventy-two hours after *All isolates were resistant to vancomycin. rods and were read as possible the first treatment, the patient was Sensitivities tested using the automated Vitek Escherichia coli. Initially, the seen by us. Visual acuity in the oper- test system (bioMerieux Vitek Inc, St Louis, Mo) patient showed improvement in ated eye was light perception with a and confirmed using the conventional disc clinical signs but developed recur- 20% hypopyon and no view of the diffusion method and the “E” test (AB Biodisk, Newark, NJ). R indicates resistant; rent inflammation after 6 weeks posterior pole. The patient under- S, sensitive. and was referred to the Bascom went pars plana vitrectomy with

Case 1. Left, Three weeks after the initial treatment with iniravitreal injections of antibiotics, the clinical examination showed recurrent hypopyon and pupillary fibrin. Visual acuity in the left eye was light perception. Right, Nine months following pars plana vitrectomy and treatment with intravitreal antibiotics, the anterior segment inflammation has resolved. Note the silicone plate posterior chamber intraocular lens positioned in the anterior chamber.

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©2000 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 intravitreal injection of ceftazidime, rate cultures yielded X maltophilia favorable clinical response to initial 2.25 mg; vancomycin hydrochlo- that was sensitive to ceftazidime but intravitreal therapy despite organ- ride, 1.0 mg; and dexamethasone resistant to all aminoglycosides, qui- ism resistance. Intravitreal injection sodium phosphate, 0.4 mg. In addi- nolones, and other ␤-lactam antibi- of antibiotics provides high initial tion, he was started on a regimen of otics. Treatment included removal of concentrations of antibiotics that are topical fortified ceftazidime, vanco- the ganciclovir implant, pars plana vi- well in excess of the minimum in- mycin, and 1% prednisolone trectomy, and administration of in- hibitory concentrations against sus- acetate, every hour, and 1% atro- travitreal and systemic ceftazidime. ceptible organisms. However, in pa- pine sulfate, 3 times daily. Vitreous Kaiser et al4 recently reported a tient 4, the organism was sensitive to cultures were positive for X malto- case of X maltophilia endophthalmi- the ceftazidime but endophthalmi- philia that was sensitive to ceftazi- tis 6 days after cataract extraction in tis still recurred. Cottingham and dime but resistant to amikacin an immunocompetent 76-year-old Forster6 hypothesized the concept of (Table 2). The initial favorable woman. The patient was initially eradication time, which was the time clinical response was followed 1 treated with pars plana vitrectomy after inoculation within which eyes week later by increasing pain, and intravitreal injections of vanco- had to be treated to be sterilized. Be- decreased visual acuity in the right mycin and tobramycin. Vitreous yond the eradication time, the organ- eye to hand movements, and aspirate culture was positive for ism load is such that pars plana vi- increased hypopyon (30%). A sec- X maltophilia that was resistant to trectomy is required in addition to ond vitreous culture was taken and both of the initially administered injection of intravitreal antibiotics. intravitreal injection of ceftazidime, antibiotics but was sensitive to Our patient 4 may represent an in- 2.25 mg, was administered and the ceftazidime, gentamicin, ciprofloxa- fected eye treated after the eradica- patient was given oral ciprofloxacin, ticarcillin, polymixin B, and tion time had elapsed. cin, 750 mg twice daily. Vitreous sulfamethoxazole-trimethoprim. Three of the 4 cases (cases 1 cultures were again positive for X However, the patient responded through 3) had visible retained lens maltophilia sensitive to ceftazidime. extremely favorably to the initial cortex that may cause intraocular in- Five days later, the patient returned treatment but had recurrence of in- flammationmimickingendophthalmi- with increasing pain and subjective flammation 6 weeks later. A second tis.7 It is also possible that the retained decrease in vision in the right eye, pars plana vitrectomy, intravitreal lens cortex may have played a role in but the results of the ocular exami- ceftazidime injection, and treat- facilitating growth of the organisms as nation were unchanged. A third ment with topical and oral cipro- has been described for postoperative course of intravitreal injections of floxacin and sulfamethoxazole- Propionibacterium endophthalmitis.8 ceftazdime, 2.25 mg, and dexa- trimethoprim sulfate was successful The antibiotic sensitivities of all methasone sodium phosphate, 0.4 in clearing the vitritis. vitreous isolates in our study are sum- mg, was administered and treat- In our study, the clinical course marized in Table 2. All 4 isolates were ment with topical fortified antibiot- of X maltophilia endophthalmitis fol- sensitive to polymixin B and sulfa- ics were continued. During the lowing cataract surgery in 4 immu- methoxazole-trimethoprim, while 3 next 3 weeks, there was significant nocompetent patients is described. of the 4 isolates were sensitive to improvement in pain and inflam- Patient 2 responded well to the ini- ciprofloxacin. All isolates were resis- mation but visual acuity remained tial intravitreal antibiotic therapy. The tant to gentamicin, while 2 of the 4 poor at hand movements because other 3 patients (cases 1, 3, and 4) isolates were sensitive to amikacin, of vitreous opacities. Pars plana had a course of recurrent infection tobramycin, and ceftazidime; there vitrectomy was performed to clear similar to previously published was no cross-resistance between ami- the vitreous opacities. Vitreous cul- cases.3,4 The duration between the kacin and ceftazidime. tures were not obtained and intra- initial treatment and the first recur- The role of systemic antibiotics vitreal antibiotic injections were rence ranged from 7 to 45 days. In inthemanagementofXmaltophiliaen- not administered. Three weeks all patients, cure was achieved by dophthalmitis is unclear. Kaiser et al4 after the second vitrectomy, the vit- pars plana vitrectomy and/or intra- used both oral ciprofloxacin and ritis resolved but visual acuity was vitreal antibiotic injection. sulfamethoxazole-trimethoprim for 20/400 OD owing to persistent cys- In a study by Stern et al,5 treatingtheirpatientwith Xmaltophilia toid macular edema. The patient reported risk factors for recurrent endophthalmitis. In accord with the returned to Nicaragua and was lost postoperative endophthalmitis in- findingsoftheEndophthalmitisVitrec- to follow-up. cluded infection with a gram- tomy Study Group9 showing no ben- negative bacillus, host immunosup- eficialeffectofsystemicantibiotictreat- Comment. The first reported case of pression, slow-growing organisms, mentinthemanagementofpostopera- X maltophilia endophthalmitis was in organisms with multiantibiotic re- tive endophthalmitis, no systemic a patient with acquired immunode- sistance, and inadequate antibiotic antibiotics were used in our study. ficiency syndrome following implan- exposure time. Antibiotic resistance Endophthalmitisassociatedwith tation of a ganciclovir implant.1 This may in part explain the recurrence in gram-negative organisms usually has patient required multiple injections the cases reported by Chen et al3 and poor visual prognosis.9,10 However, of amikacin and ciprofloxacin hy- Kaiser et al4 and cases 1 and 3 in our some gram-negative organisms may drochloride with only partial re- study. The case by Kaiser et al4 and be less virulent, cause somewhat sponse. Two different vitreous aspi- patient 1 in our case series did show delayed-onset endophthalmitis, and

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©2000 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 have a better visual prognosis.11 De- ing routine RFNL photography per- spitethehighrecurrencerate,endoph- Pseudodefects of the formed because of suspected glau- thalmitis caused by X maltophilia Retinal Nerve Fiber Layer coma, a positive family history of seems to be in the latter category since Examined Using Optical glaucoma (9 patients), or in screen- the visual acuity outcomes after treat- Coherence Tomography ing for glaucoma by the Finnish ment were generally favorable. Glaucoma Patient Association (4 Our case series and the previ- patients). In 4 eyes found during ously reported cases demonstrate Glaucoma destroys the ganglion cell glaucoma screening, all patient data that X maltophilia endophthalmitis axons in the retina and may pro- were unknown, as only the screen- may have a persistent and recur- duce localized and/or diffuse dam- ing photographs were available. Five rent clinical course even when the age of the retinal nerve fiber layer of the remaining 9 patients were high organism is sensitive to the intravit- (RNFL). Unlike diffuse damage, lo- myopes (spherical equivalent of real antibiotics used. Hence, it is im- calized defects are easy to detect. At −7.0, −9.25, −10.0, −10.0, and −16.5 portant to follow up these patient the location of the RNFL defect the diopters [D]), 2 were mild myopes closely for recurrence, possibly re- normal striated pattern of RNFL dis- (−1.25 and −2.25 D), and 2 pa- peating treatment with intravitreal appears and the localized defect is tients were hyperopes (+6.5 and +2.0 antibiotics and pars plana vitrec- well outlined against the surround- D). Seven of 9 patients had ocular tomy when indicated. ing healthy nerve fiber bundles.1 Al- hypertension (range, 23-28 mm Hg). though single or multiple slitlike de- Except for the pseudodefects, the pa- Nauman A. Chaudhry, MD fects are probably not a sign of tients with ocular hypertension had Harry W. Flynn, Jr, MD abnormality, they may sometimes be otherwise normal RNFL, normal op- William E. Smiddy, MD misinterpreted as a localized RNFL tic disc appearance, and normal Darlene Miller, MS, MPH defect. This study demonstrates an- Humphrey 30-2 visual field re- Miami, Fla other RNFL finding to be differenti- sults. Five of these 7 patients also had ated from a true localized RNFL de- follow-up ranging from 4 to 10 years. Corresponding author: Harry W. Flynn, fect, ie, what we call a “pseudodefect” One of these 5 patients developed Jr, MD, Bascom Palmer Eye Institute, of the RNFL. glaucoma during the follow-up pe- 900 NW 17th St, Miami, FL 33136 riod that subsequently resulted in (e-mail: [email protected]). Report of Cases. When routine enlargement of optic disc cupping, RNFL photographs were examined, diffuse thinning of the RNFL, and a 1. Marshall W, Keating MR, Anhalt JP, Steckel- pseudodefects were detected in a to- glaucomatous visual field defect. In berg JM. Xanthomonas maltophilia: an emerging nosocomial pathogen. Mayo Clin Proc. 1989; tal of 13 patients (Figure 1). Four this progressive case, the shape of the 64:1097-1104. patients were found during glau- pseudodefect did not change; how- 2. Manfredi R, Nanetti A, Ferri M, Chiodo F. Xan- thomonas maltophilia: an emerging pathogen in coma screening and no information ever, it became less easily visible with patients with HIV disease. Int J STD AIDS. 1998; was available from the Finnish Glau- overall thinning of the RNFL. 9:201-207. coma Patient Association. The re- The pseudodefects were found 3. Chen S, Stroh EM, Wald K, Jalkh A. Xan- thomonas maltophilia endophthalmitis after im- maining 9 patients (7 female and 2 along the major retinal blood ves- plantation of sustained-release ganciclovir. Am male) had a mean age of 62 years (age sels. Within 1 to 4 disc diameters J Ophthalmol. 1992;114:772-773. range, 41-75 years). We also had the from the optic disc margin, they 4. Kaiser GM, Tso PC, Morris R, McCurdy D. Xan- thomonas maltophilia endophthalmitis follow- opportunity to measure 6 patients looked like oblong or braid-shaped ing cataract extraction. Am J Ophthalmol. 1997; with RNFL pseudodefects using Op- chinks or cracks within the normal 123:410-411. 5. Stern GA, Engel HM, Driebe WT. Recurrent tical Coherence Tomography (Zeiss- RNFL structure (Figure 1). In 3 eyes 2 postoperative endophthalmitis. Cornea. 1990; Humphrey, San Leandro, Calif). Sev- these pseudodefects could be fol- 9:102-107. eral optical coherence tomographic lowed far into the periphery (up to 6. Cottingham AJ, Forster RK. Vitrectomy in endophthalmitis: results of a study using vitrec- scans were taken across the pseudo- 4 disc diameters temporal to the tomy, intraocular antibiotics, or a combination defect. Using a prototype software ver- macula) where the pseudodefect no of both. Arch Ophthalmol. 1976;94:207-208. sion, an estimate of the mean thick- longer looked like a chink but had 7. Irvine WD, Flynn HW Jr, Murray TG, Rubsa- men PE. Retained lens fragments after phaco- ness of the RNFL at the site of the a flat, beaten appearance. In 1 pa- emulsification manifesting as marked intra- pseudodefect was compared with the tient the pseudodefect was seen in ocular inflammation with hypopyon. Am J Ophthalmol. 1992;114:610-614. mean thickness of the adjacent nor- the inferior nasal retina; all others 8. Winward KE, Pflugfelder SC, Flynn HW Jr, mal retina on both sides of the pseu- were located temporal to the optic Roussel TJ, Davis JL. Postoperative Propioni- dodefect (Figure 2). The mean of 3 disc and/or the macula. In 2 pa- bacterium endophthalmitis. Ophthalmology. 1993; 100:447-451. measurements was used for each lo- tients pseudodefects were found in 9. Endophthalmitis Vitrectomy Study Group. Re- cation. The optic disc size of the 6 eyes both eyes. sults of the Endophthalmitis Vitrectomy Study: was measured using a Heidelberg In 5 of 6 patients the optical co- a randomized trial of immediate vitrectomy and intravenous antibiotics for the treatment of post- Retina Tomograph (Heidelberg En- herence tomographic scan showed a operative bacterial endophthalmitis. Arch Oph- gineering, Heidelberg, Germany).3 In- thinning of the RNFL at the pseudo- thalmol. 1995;113:1479-1496. 10. Irvine WD, Flynn HW Jr, Miller D, Plugfelder SC. formed consent was obtained from all defect. The mean ± SD thickness of Endophthalmitis caused by gram-negative organ- 6 patients who were examined. the RNFL was 132 ± 49 µm at the isms. Arch Ophthalmol. 1992;110:1450-1454. pseudodefect, 220 ± 49 µm on the 11. Aaberg TM Jr, Rubsamen PE, Joondeph BC, Flynn HW Jr. Chronic postoperative gram-negative en- Comment. Pseudodefects were temporal side of the pseudodefect, dophthalmitis. Retina. 1997;17:260-261. found in a total of 13 patients dur- and 203 ± 70 µm on the nasal side of

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©2000 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 neovascularization, or clumping of the retinal pigment epithelium associated with the pseudodefect. Their results of fluorescein angiography confirmed the integrity of Bruch’s membrane. They sug- gested that the pseudodefect may be associated with a breakdown of in- traretinal neural connections and may later lead to an RNFL defect. In the 1 progressive case of our series the shape of the pseudodefect itself did not change; however, it became less easily visible with advancing glaucomatous damage. It is probable that we need his- topathological studies to learn more about the so far unknown etiology Figure 1. Within 1 to 4 disc diameters from the optic disc margin the pseudodefects of the retinal nerve of the pseudodefects. However, it is fiber layer look like oblong or braid-shaped chinks or cracks in the normal retinal nerve fiber layer structure (small arrows). Further in the periphery, the pseudodefect has a flat, beaten appearance important clinically to recognize the (large arrow). existence of pseudodefects and dif- ferentiate them from true RNFL de- 1992 Chihara and Chihara5 defects in the diagnosis and fol- scribed 3 patients with what they low-up of subjects with glaucoma. called a cleavage of the RNFL. They reported that the cleavage was asso- Anja Tuulonen, MD, PhD ciated with high myopia (−14, −14, Ilgaz S. Yalvac, MD and −15 D) and postulated that the Oulu, Finland number of axons might be insuffi- cient to cover the enlarged posterior The authors have no commercial or segment of these myopic eyes. All of proprietary interest in the devices or their patients were younger than 35 companies mentioned in this article. years. They did not find a cleavage in Presented in part at the 30th any of 144 emmetropic or hyperopic Turkish National Meeting of Ophthal- eyes. The cleavage was unassociated mology, Antalya, Turkey, September with any visual dysfunction mea- 15, 1996, and the Association of Vi- sured with automated perimetry. sion Research in Ophthalmology meet- In our larger number of pa- ing, Fort Lauderdale, Fla, May 15, tients we found several differences 1998. and new findings compared with the Figure 2. An Optical Coherence Tomographic Reprints: Anja Tuulonen, MD, previously published Japanese cases, PhD, Department of Ophthalmology, (Zeiss-Humphrey, San Leandro, Calif) image of ie, (1) although most frequent in high a retinal nerve fiber layer pseudodefect (arrow) University of Oulu, FIN-90220 Oulu, adjacent to the blood vessel. myopes, pseudodefects were found Finland (e-mail: anja.tuulonen@ also in hyperopes and mild myopes, oulu.fi). pseudodefect. The differences of the (2) our patients were all older than retinal thickness values at the pseu- 40 years, (3) in 2 patients the changes 1. Tuulonen A, Airaksinen PJ. Funduscopic and dodefects compared with the aver- were seen bilaterally, (4) the mean photographic characteristics of the retinal nerve 2 fiber layer in glaucoma. In: Podos SM, Yanoff M, age retinal thickness values on ei- optic disc size of 1.4 mm of the eyes Kaufman PL, Thomas W, eds. Textbook of Oph- ther side of the pseudodefect were with pseudodefects was smaller com- thalmology. Glaucoma: Philadelphia, Pa: Mosby– Year Book Inc; 1994:4.12-4.19. 212, 136, 111, 38, 32, and −53 µm pared with our previously reported 2. Schuman JS, Hee MR, Pulifiato CA, et al. Quan- 2 4 (mean difference, 79 µm). The re- mean disc size of 2.1 mm , and (5) tification of nerve fiber layer thickness in nor- spective differences were 70%, 56%, the mean decrease in retinal thick- mal and glaucomatous eyes using optical coherence tomography: a pilot study. Arch Ophthalmol. 49%, 22%, 21%, and −30% (mean dif- ness was 79 µm (37%) at the pseu- 1995;113:586-596. ference, 37%). The mean ± SD optic dodefect, which is larger than the 3. Burk ROW, Rohrschneider K, Takamoto T, Vo¨lc- disc area of the 6 eyes using the mean difference of 39 µm reported ker HE, Schwartz B. Laser scanning tomography and stereophotogrammetry in three- Heidelberg Retina Tomograph between glaucomatous and normal dimensional optic disc analysis. Graefes Arch Clin measurements was 1.40 ± 0.2 mm2 eyes.2 Exp Ophthalmol. 1993;231:193-198. 2 5 4. Tuulonen A, Airaksinen PJ. Optic disc size in ex- (reference range, 1.1-1.6 mm ), Chihara and Chihara exam- foliative, primary open angle, and low-tension which is smaller than the mean of our ined the 3 eyes with pseudodefect glaucoma. Arch Ophthalmol. 1992;110:211-213 patients with glaucoma (2.1 mm2).4 using dark-field imaging of the scan- 5. Chihara E, Chihara K. Apparent cleavage of the retinal nerve fiber layer in asymptomatic eyes We found 1 previous report on ning laser ophthalmoscopy and did with high myopia. Graefes Arch Clin Exp Oph- pseudodefects in the literature. In not find any lacquer crack lesions, thalmol. 1992;230:416-420.

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©2000 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 suresincludedchemotherapycyclede- During the course of therapy, Complications of Systemic lays, adjustment of chemotherapy the 12 patients had a total of 91 ex- Chemotherapy as doses owing to side effects, delays in aminations under anesthesia sched- Treatment of planned examinations under anes- uled, 16 (18%) of which were de- Retinoblastoma thesia, unplanned hospital admis- layed an average of 10 days (range, sions, febrile episodes, myelosup- 1-21 days). Seven patients (58%) had Retinoblastoma is the most com- pression, transfusions, and port- at least 1 examination under anes- mon intraocular tumor in children.1 related complications. thesia delayed. Causes of delay of ex- Historically, the treatment of retino- Five (42%) of the 12 patients amination under anesthesia in- blastoma was enucleation.1 How- were male and all 12 had no family cluded neutropenia in 11 (69%) of 16 ever, improvements in diagnosis and history of retinoblastoma. The mean patients, febrile episode in 7 (44%) treatment of retinoblastoma have led age at diagnosis was 17 months (age of 16 patients, and thrombocytope- not only to a survival rate well over range, 2-66 months); the mean du- nia in 4 (25%) of 16 patients. 90%,1 but also to an increasing abil- ration of chemotherapy was 5.9 Nine patients (75%) had at least ity to offer globe conservation as a months. One of the 12 patients had 1 unplanned hospital admission secondary goal of therapy. Globe- extraocular disease. (mean, 1.7 admission; reference conserving therapies include cryo- All of the patients received car- range, 0-4 admissions) during the therapy, laser photoablation, hyper- boplatin (20 mg/kg for patients Ͻ12 course of chemotherapy. The rea- 2 thermia, and plaque radiotherapy for months, 550-600 mg/m body sur- sons for unplanned hospital admis- smaller tumors, and external beam ra- face area for patients Ͼ12 months) sions included neutropenia (5 pa- diation and systemic chemotherapy and etoposide phosphate (5 mg/kg if tients, 60%), fever (4 patients, 50%), for larger tumors not amenable to lo- the patient was Ͻ12 months, 150 and thrombocytopenia (4 patients, 2 cal control.2 mg/m body surface area if the 45%) Some patients had more than Recently, multiple-agent che- patient was Ͼ12 months), 9 (75%) 1 problem leading to their hospital motherapy with etoposide phos- received vincristine sulfate (0.05 admission. Five patients (42%) re- phate, carboplatin, and vincristine mg/kg if the patient was Ͻ12 months, quired a transfusion of platelets; 3 2 sulfate combined with transpupil- 1.5-2 mg/m body surface area if the patients (25%) needed a transfu- lary hyperthermia has been demon- patient was Ͼ12 months) and 4 sion of packed red blood cells dur- strated to achieve excellent local con- (33%) also received cyclosporine (5 ing the course of therapy. trol of retinoblastoma.3 Further, mg/kg per hour bolus for 2 hours be- Each patient had a central in- systemic chemotherapy spares the fore chemotherapy started, then a 1.5 travenous port placed under gen- patient the risk of craniofacial ab- mg/kg per hour infusion over the next eral anesthesia at the outset of normalities and may eliminate or de- 30 hours if the patient weighed Ͻ12 therapy. Surgical time for port place- crease the risk of secondary tumors kg, adjusted to 4 mg/kg per hour and ment averaged 47 minutes (range, that have been associated with ex- 1.25 mg/kg per hour, respectively, if 35-90 minutes). Two of the patients ternal beam radiation.4 However, the patient weighed 12-30 kg, and ad- underwent unplanned port removal systemic chemotherapy employed justed to 3 mg/kg per hour, and 1.0 secondary to complications (infec- for retinoblastoma has been associ- mg/kg per hour if the patient weighed tion and exposure). ated with adverse events such as my- Ͼ30 kg). The 1 patient who had ex- None of the patients required elosuppression and subsequent intraocular tumor extension also re- discontinuation of the treatment fections and need for transfusion ceived intrathecal treatment with a course secondary to treatment- of blood products.5 To our knowl- combination of methotrexate, hydro- associated morbidity. Outstanding edge, the incidence of such compli- cortisone sodium succinate, and cy- tumor response was achieved cations and their effect on treat- tarabine. The patients underwent a in all patients. No patient in our ment remain unknown. This study mean of 7.2 cycles of chemotherapy series required enucleation or evaluates the adverse events and (range, 4-10 cycles). radiotherapy owing to failure of resultant alterations in treatment Nine patients (75%) had at least the planned treatment with sys- protocol during the treatment of reti- 1 cycle of chemotherapy delayed temic chemotherapy. noblastoma with systemic chemo- during the course of therapy. The 12 therapy. patients underwent a total of 86 Comment. Although the use of cycles of chemotherapy, 17 (19.8%) systemic chemotherapy for retino- Report of Cases. The study protocol of which were delayed an average of blastoma is not amenable to local was approved by the Institutional Re- 9 days (range, 1-30 days). Chemo- treatment but is associated with view Board of the University of Miami therapy was often delayed owing to excellent local tumor control, School of Medicine, Miami, Fla. The a combination of factors, including adverse events are likely to compli- medicalrecordsofallpatientswithreti- neutropenia in 11 (65%) of 17 pa- cate the course of treatment. Even noblastoma evaluated at Bascom tients, thrombocytopenia in 6 (35%) though these adverse events are Palmer Eye Institute, Miami, and of 17 patients, and febrile episode in treatable and did not result in the treated with systemic chemotherapy 5 (29%) of 17 patients. Four (33%) cessation of therapy, physicians at Jackson Memorial Hospital, Miami, of the 12 patients had doses of che- administering the treatment and between July 1, 1995, and May 31, motherapy reduced secondary to counseling the families of affected 1999, were reviewed. Outcome mea- treatment-related morbidity. patients should be aware of the

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©2000 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 potential complications and should nystagmus worsened on left gaze. communicate the risks to the families. Persistent Hyperplastic Corneal diameters were 8 mm OD An additional consideration Primary Vitreous and 10 mm OS. Biomicroscopic ex- in planning future systemic chemo- Associated With amination of the right eye revealed therapy regimens for patients Septo-optic-pituitary a clear cornea, and a shallow, but with retinoblastoma is the incorp- formed, anterior chamber. Neither Dysplasia and oration of granulocyte colony- iris vessels nor elongated ciliary pro- stimulating factor (Neupogen; Schizencephaly cesses were noted. A fibrovascular Amgen, Thousand Oaks, Calif) in plaque on the superonasal retrolen- the treatment plan. Granulocyte Persistent hyperplastic primary vit- tal surface funneled to a vascular colony-stimulating factor has been reous (PHPV), a form of persistent fe- band that extended on to a small op- demonstrated to have promyelo- tal vasculature, occurs infrequently tic disc. Macular anatomy was ab- cytic activity and may help to de- with systemic conditions.1 We re- sent in this eye (Figure 2). crease the incidence of myelosup- port the novel association of unilat- The left eye was remarkable for pression, infection, and need for eral PHPV with septo-optic-pitu- a normal anterior segment, en- transfusion of blood products in itary dysplasia (SOPD) and ipsilateral gorged retinal veins, and a small, pale these patients.6 schizencephaly. optic disc with a double-ring sign. Further information concern- Because improvement in visual func- ing systemic chemotherapy- Report of a Case. A full-term fe- tion with surgical intervention was associated morbidity among pa- male neonate was born to a 17-year- not expected, only periodic fol- tients with retinoblastoma should old primigravid woman by cesar- low-up was recommended. become available with the results ean delivery. On the third day of life, of the international clinical trial hypoglycemia and hypotonia raised Comment. Persistent hyperplastic funded by the National Cancer In- the suspicion of sepsis, for which in- primary vitreous refers to a form of stitute to evaluate systemic chemo- travenous antibiotic therapy was ad- persistent fetal vasculature in which reduction in the management of ministered. Microbiologic cultures the posterior tunica vasculosa len- patients with large bilateral retino- were negative for organisms. The pa- tis (or posterior fetal fibrovascular blastomas. tient’s condition stabilized and the sheath) and the hyaloid artery fail to neonate was discharged from the regress.1 Although traditionally a Matthew S. Benz, MD hospital. sporadic, unilateral, and isolated Ingrid U. Scott, MD, MPH On the ninth day of life, the pa- finding, PHPV also has been re- Timothy G. Murray, MD tient was found ashen and unre- ported in trisomy 13, Norrie dis- Deborah Kramer, MD sponsive; she had suffered a grand ease, Warburg syndrome, inconti- Stuart Toledano, MD mal seizure. On admission to a neo- nentia pigmenti, cerebro-oculo- Miami, Fla natal intensive care center, the pa- dysplasia-muscular dystrophy,1 and tient was lethargic, hypotonic, hy- fetal alcohol syndrome.2 Malforma- Corresponding author: Timothy G. poglycemic (1.270 mmol/L [23 mg/ tions of the macula, such as hypo- Murray, MD, Bascom Palmer Eye In- dL]), and hyperbilirubinemic (239.4 plasia in our patient, may occur.1 stitute, 900 NW 17th St, Miami, FL µmol/L [14.0 mg/dL]). Magnetic Septo-optic-pituitary dyspla- 33136 (e-mail: [email protected] resonance imaging scans revealed an sia (de Morsier syndrome) refers to .miami.edu). absent septum pellucidum, poste- the variable constellation of absent rior ectopic pituitary gland, absent septum pellucidum, complete or infundibulum, right closed lip schiz- partial thinning of the corpus callo- 1. Tamboli A, Podgor MJ, Horm JW. The inci- encephaly, cortical dysplasia, and sum, hypoplastic anterior visual dence of retinoblastoma in the United States, 1974 through 1985. Arch Ophthalmol. 1990;108: ventriculomegaly (Figure 1). Se- pathways, and pituitary hormone de- 128-132. rum endocrinologic evaluation dis- ficiency.3,4 Endocrinologic prob- 2. Shields CL, Shields JA, Needle M, et al. Com- closed a low thyrotropin level (4.6 lems may be life-threatening as in bined chemoreduction and adjuvant treatment for intraocular retinoblastoma. Ophthalmology. µIU/mL), low total thyroxine level our patient, whose corticotropin de- 1997;104:2101-2111. (50 nmol/L [3.9 µg/dL]), low morn- ficiency caused apnea, hypotonia, 3. Gallie BL, Budning A, DeBoer G, et al. Chemo- Ͻ therapy with focal therapy can cure intraocular ing cortisol level ( 55 nmol/L), and seizures, prolonged jaundice, and retinoblastoma without radiotherapy. Arch Oph- subnormal response to corticotro- hypoglycemia. Absent pituitary in- thalmol. 1996;114:1321-1328. pin stimulation (0.66 pmol/L). The fundibulum on the magnetic reso- 4. Desjardins L, Haye C, Sclieninger P, et al. Sec- ond non-ocular tumours in survivors of bilat- patient was treated for thyrotropin nance imaging scan correlates with eral retinoblastoma: a thirty-year follow-up. Oph- deficiency and corticotropin defi- concurrent endocrinologic defi- thal Paediatr Genet. 1991;12:145-148. ciency with levothyroxine sodium ciency, while an ectopic posterior pi- 5. Murphee AL, Villablanca JG, Deegan WF III, et al. Chemotherapy plus local treatment in the and hydrocortisone, respectively. tuitary, seen as an intense nodule in management of intraocular retinoblastoma. Arch During ophthalmic examina- T1-weighted images, may have spar- Ophthalmol. 1996;114:1348-1356. 3 6. Rusthoven J, Bramwell V, Stephenson B. Use of tion on the 13th day of life and again ing of posterior pituitary function granulocyte colony-stimulating factor in pain the seventh week of life, the in- (Figure 1). tients receiving myelosuppressive chemo- fant did not fixate but briefly fol- Schizencephaly is a cerebral therapy for the treatment of cancer: Provincial Systemic Treatment Disease Site Group. Can- lowed light. Pupils sluggishly re- hemisphere migration anomaly in cer Prev Control. 1998;2:179-190. acted to light and a left-sided beating which an abnormal gray matter–

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Figure 1. T1-weighted magnetic resonance images of the head reveal persistent hyperplastic primary vitreous in the right eye (white arrowhead) (A); posterior ectopic pituitary gland (small arrow), absent infundibulum (large arrow), absent septum pellucidum (small white arrowhead) (B and C); and right closed lip schizencephaly (black arrowhead) (D).

A B

Figure 2. A, Fundus photograph of the right eye shows persistent hyaloid artery extending on to a hypoplastic optic disc. B, Fundus photograph of the left eye shows enlarged retinal veins and a hypoplastic optic disc with double-ring sign.

lined cleft extends through the ce- clear. Persistent fetal vasculature has connections,3 or vascular insult to a rebral hemisphere from the lateral been postulated to be an arrest in fe- developmental field during the first ventricletothecorticalsurface.Schiz- tal intraocular vascular develop- trimester of embryogenesis.5 Al- encephaly may accompany SOPD ment.1 Septo-optic-pituitary dyspla- though a teratogenic history was not and can lead to seizure disorder and sia has been postulated to result from elicited in our patient, coincident op- mental retardation.3 supernormal regression of axons,4 tic nerve hypoplasia with PHPV2 and The pathogeneses of PHPV, disrupted migration of neurons and coincident SOPD and schizen- SOPD, and schizencephaly are un- axons with failure to make target cephaly have been reported in pa-

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©2000 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 tients with a maternal history of ges- tational substance abuse.5 Our case of unilateral PHPV with SOPD and ipsilateral schizencephaly is a novel and intriguing association.

Andreas Katsuya Lauer, MD Martin J. Balish, MD Earl A. Palmer, MD Portland, Ore

This investigation was supported by unrestricted fund from the Research to Prevent Blindness Inc, New York, NY. The authors have no proprietary interest in any material relating to this article. Corresponding author: Andreas Katsuya Lauer, MD, Casey Eye Insti- tute, Oregon Health Sciences Center, 3375 SW Terwilliger Blvd, Portland, OR 97201-4197.

1. Goldberg MF. Persistent fetal vasculature (PFV): an integrated interpretation of sign and symptoms associated with persistent hyperplastic primary vitreous (PHPV): LIV Edward Jackson Memorial Figure 1. Findings from ophthalmoscopy (right eye) demonstrate retinal cotton-wool lesions scattered Lecture. Am J Ophthalmol. 1997;124:587-626. throughout the posterior pole. The site of the retinal infarctions differs from the localization of choroidal 2. Stromland K, Pinazo-Duran MD. Optic nerve hy- perfusion changes. Two small spots were seen superior to the macula (arrow), an area that did not poplasia: comparative effects in children and rats exhibit any choroidal alteration. The perifoveal capillary net was perfused in early-phase fluorescein exposed to alcohol during pregnancy. Teratol- angiography and did not present any ischemia-related leakage in late-phase fluorescein angiography. ogy. 1994;50:100-111. 3. Brodsky MC, Glasier CM. Optic nerve hypoplasia: clinical significance of associated central nervous system abnormalities on magnetic resonance im- as choroidal nonperfusion. Results and small retinal hemorrhages were aging. Arch Ophthalmol. 1993;111:66-74. of scanning laser ophthalmoscope found scattered throughout the pos- 4. Lambert SR, Hoyt CS, Narahara MH. Optic nerve microperimetry revealed central sco- terior pole in both eyes (Figure 1). hypoplasia. Surv Opthalmol. 1987;32:1-9. 5. Dominguez R, Aguirre Vila-Coro A, Slopis JM, tomas corresponding to choroidal The patient was not diabetic, and his Bohan TP. Brain and ocular abnormalities in in- perfusion defects. Cotton-wool spots blood pressure levels have never been fants with in utero exposure to cocaine and other street drugs. AJDC. 1991;145:688-695. and retinal hemorrhages disap- elevated. Other systemic causes of peared during therapy over a cotton-wool spots were excluded by 6-month period, but visual impair- findings from extensive laboratory ex- ment and choroidal ischemia per- amination. Two months later, his vi- Combined Choroidal and sisted. In addition to retinopathy, sual acuity decreased to 20/50 OD and Retinal Ischemia During IFN therapy may also induce per- remained unchanged in his left eye. Interferon Therapy: sistent choroidal perfusion changes Results of fluorescein angiography Indocyanine Green associated with scotomization. showed a central area of complete ab- Angiographic and Our patient was seen for blurred senceofchoroidalperfusionwithover- Microperimetric Findings vision in both eyes and reading diffi- lying intact retinal perfusion and no culty for several months. Findings alteration of the perifoveal capillary This article presents findings from from the patient’s medical history re- net in early-phase fluorescein angiog- indocyanine green angiography vealed renal cell carcinoma, for which raphy (Figure 2, A and B). Late-phase (ICGA) and microperimetry in a he had undergone nephrectomy 3 fluorescein angiography showed ve- patient with interferon (IFN)- years earlier. Treatment with IFN alfa- nous dilatation and retinal vessel leak- associated combined choroidal and 2b was administered for metastasis of age in both eyes (Figure 2, C). The retinal perfusion deficits. the lung with an initial dose of 2 ϫ 106 ICGArevealedawell-demarcatedarea IU subcutaneously and increased to of confluent and persistent choroidal Report of a Case. A 40-year-old man the continuos dose of 10 ϫ 106 IU 5 filling defects (Figure 3, A). The char- was seen for central scotomas and times per week. His general condition acteristic ICG pattern of the capillary blurred vision during treatment with was otherwise good, and he did not and arteriolar net was missing. Find- IFN alfa-2b for metastatic renal cell take any other medications. Ocular ings from objective testing using scan- carcinoma. Findings from retinal ex- symptoms were noted roughly 1 ning laser ophthalmoscope micro- amination included cotton-wool spot month after initiation of IFN alfa-2b perimetry revealed central and para- formation and small hemorrhages. therapy.Oninitialexamination,visual central scotomas (Figure 4) precisely Findings from fluorescein and ICGA acuity was 20/20 OU. On ophthalmo- corresponding to the 2 areas of cho- demonstrated areas of retinal as well scopicexamination,cotton-woolspots roidal hypofluorescence consistent

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Figure 2. A, Findings from early-phase fluorescein angiography (right eye) showing delineation of choroidal filling defects (within arrows) with overlying intact retinal vascular perfusion and no alterations of the perifoveal capillary net. B, Subsequent fluorescein angiography findings (right eye) depict a central area of complete absence in choroidal perfusion (within arrows); overlying retinal vessels are intact and exhibit no ischemic or exudative alteration. C, Late-phase fluorescein angiography findings (right eye) show leakage of large retinal veins.

A B

Figure 3. A, Results of indocyanine green angiography (ICGA) (right eye) demonstrate a well-demarcated area of confluent choroidal perfusion defects (within arrows). In early phases of ICGA (15 seconds), the pattern of the capillary and arteriolar net is missing. A laser scanning system (Heidelberg Retina Angiograph; Heidelberg Engineering, Heidelberg, Germany) was used for ICGA imaging. B, In late phases of ICGA (4 minutes), most of the area of choroidal hypofluorescence is reduced by leakage from the borders of the lesion where choriocapillary filling and physiological leakage from fenestrated capillaries occurs. Two areas with relative hypofluorescence (arrows) persist throughout the late-phase ICGA and are identical with the localization of defects found by microperimetry.

with choroidal ischemia during late- it is used to treat human neoplasms, To our knowledge, choroidal phase ICGA (Figure 3, B). A slight de- including metastatic renal cell carci- perfusion changes have not been decrease of the Arden ratio was found by noma. Interferon-associated retinopa- scribed in the literature until now wholeelectroretinography.Withinthe thy has been described previously, and are documented for the first time initial follow-up period of 6 months, mainly in the Japanese literature.1,2 in a patient undergoing prolonged the cotton-wool spots and the retinal Typicalretinalfindingsincludecotton- systemic IFN therapy. The patient hemorrhages disappeared. However, wool spots, hemorrhages, and micro- had symptoms of focal retinal cap- there was no recovery of the central aneurysms. Retinal ischemia may be illary dropout as manifested by cot- choroidal perfusion changes. Func- observed in affected areas by fluores- ton-wool spots. However, there were tional defects persisted over a 1-year cein angiography. Other ocular find- no retinal infarctions seen within follow-up period, and visual acuity re- ings included conjunctival hemor- the area of choroidal nonperfusion mained 20/63 OD. rhage, central retinal vein occlusion, itself, and the perifoveal capillary branch retinal artery occlusion, aggra- perfusion was intact (Figure 2, A). Comment. Interferon alfa inhibits vas- vation of diabetic retinopathy, optic Choroidal filling defects were sub- cular endothelial cell proliferation and disc edema, oculomotor nerve paraly- stantiated by ICGA (Figure 3) and reveals antitumor activity. Therefore, sis, and hypertrichosis.1,2 appeared to be responsible for vi-

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©2000 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 anti-IFN-alfa antibody titres during interferon therapy [letter]. Lancet. 1987;2:635-636. 4. Cogan DG. Ocular involvement in dissemi- nated intravascular coagulopathy. Arch Ophthal- mol. 1975;93:1-8. 5. Stern WH, Ernest JT. Microsphere occlusion of the choriocapillaris in rhesus monkeys. Am J Oph- thalmol. 1974;78:438-448.

Tear of the Retinal Pigment Epithelium and Serous Retinal Detachment in a Case of IgA Nephropathy After Renal Transplantation

Central serous chorioretinopathy has been reported to be independently as- Figure 4. Findings from scanning laser ophthalmoscope microperimetry (right eye) reveal central and sociated with a retinal pigment epithe- paracentral scotomas corresponding to the areas of reduced choroidal perfusion; retinal sensitivity was 1 lost for stimuli of 11 dB, indicating intensive scotomization (green indicates seen stimuli; red, invisible lial (RPE) tear and renal transplan- stimuli). tation.2 To our knowledge, the association of an RPE tear, central serous sual impairment based on micro- choriocapillarisbyanarterialroutedid chorioretinopathy, and renal trans- perimetry. Electrophysiological find- not result in detachments experimen- plantation, however, has not been re- ings supported the presence of tally.5 Arterial choroidal occlusion is ported in the English-language litera- photoreceptor damage, which is re- most likely responsible for intensive ture.Additionally,RPEtearusuallyoc- sponsible for the central functional functional defects. However, choroi- cursatonesideoftheRPEdetachment. defect documented by scanning la- dalperfusionchangesandphotorecep- We report a case in which the RPE tear ser ophthalmoscope microperim- tor function did not recover during occurred at the center of the RPE de- etry. The central and paracentral sco- long-term follow-up. tachment and is associated with cen- tomas corresponded in size and Our observation suggests that tral serous chorioretinopathy in a pa- location to 2 persisting choriocap- patients demonstrating retinopathy tient with IgA nephropathy after re- illary perfusion defects delineated by during IFN therapy should care- nal transplantation. ICGA. As reported by other au- fully be examined by ICGA and cen- thors, symptoms of retinal vascu- tral field testing to recognize addi- Report of a Case. A 39-year-old Chi- lopathy subsided spontaneously in tional choroidal nonperfusion. Since nese man was initially seen by us with our patient; the choroidal defects, there is evidence that vaso-occlu- a2-monthhistoryofflashesinhisright however, did not resolve. sion might not be restricted to reti- eye. He had a history of IgA nephropa- The pathogenesis of IFN- nal capillaries, the risk of ischemia oc- thy requiring renal transplantation 6 associated vasculopathy is unclear. It curring within other organ systems months earlier. A combined regimen is known that up to 10% of patients should be taken into account. of oral cyclosporine and prednisolone treated with recombinant IFN alfa was given to prevent graft rejection. produce autoantibodies.3 It is there- Hans Hoerauf, MD On ophthalmic examination,the pa- fore postulated that IFN may cause Ursula Schmidt-Erfurth, MD tient’s best-corrected visual acuities deposition of immune complexes in Mary Asiyo-Vogel, MD were 20/50 OD and 20/30 OS. Intra- retinal vessels.2 However, capillary- Horst Laqua, MD ocular pressure in both eyes was nor- type damage is suspected in IFN reti- Lu¨beck, Germany mal. Slitlamp examination showed no nopathy, while choroidal nonperfu- abnormalities. Funduscopic exam- sion is more likely owing to occlusion The authors have no commercial, pro- ination of his right eye revealed a of larger-caliber vessels. prietary, or financial interest in any crescent-shaped RPE tear with rolls of Occlusive choroidopathy was research or devices described in this RPE along both edges, along the in- seen in malignant hypertension and study. ferotemporal arcade (Figure 1). Ad- Harada disease and was associated his- Reprints: Hans Hoerauf, MD, De- ditionally, there was exudative retinal topathologically with fibrin platelet detachment inferior to the macula 4 partment of Ophthalmology, Medical clots in the choriocapillaris. Another University Lu¨beck, Ratzeburger Allee when the patient was sitting upright; possible origin of choroidal thrombo- 160, 23538 Lu¨beck, Germany. andthemaculawasinvolvedwhenthe sis could be the underlying renal cell patient was supine. A few small RPE carcinoma,whichmighthavetriggered 1. Hayasaka S, Nagaki Y, Matsumoto M, Sato S. In- detachments outside the macular re- terferon-associated retinopathy. Br J Ophthal- an embolic event by platelet or tumor mol. 1998;82:323-325. gion were also found in his left eye. clots. Venous choroidal thrombosis 2. Guyer DR, Tiedeman J, Yannuzzi A, et al. Inter- Fluorescein angiography of the right mostly induced serous retinal detach- feron-associated retinopathy. Arch Ophthalmol. eye demonstrated a hyperfluorescent 1993;111:350-356. ment,whichwasnotpresentinourpa- 3. von Wussow P, Freund M, Block B, Diedrich H, lesion measuring about 7 ϫ 5 disc di- tient. However, embolization of the Poliwoda H, Deicher H. Clinical significance of ameters, lined by 2 almost parallel hy-

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©2000 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 pofluorescent bands (Figure 2, left). Comment. Krishan et al,3 using a one side. In our patient, the RPE tear There was a point of leakage located metal plate model, demonstrated that occurred at the center of the detach- at the inferonasal margin of the RPE the bending stress along the RPE de- ment. This might be due to uneven tear during the early phase, which tachment was inversely propor- thickness or strength of the RPE layer. leaked profusely during the later stage tional to the radius of curvature. The Gradual weakening or thinning of the (Figure 2, right). Electroretinography radius of curvature at the margin of RPE layer at the center of the detach- and electro-oculography of the right the detachment was much smaller ment might have rendered it unable eye were abnormal. Amplitudes of than that at the center. Hence, the to sustain high mechanical stresses. the b-wave were 30.5 µV in the right bending stress at the edge was greater Whether a steroid administered for eye and 133.1 µV in the left eye. The than that at the center of the RPE systemic effect or IgA nephropathy Arden ratios were 1.29 OD and 2.24 detachment, which explained why itself predisposes the RPE weakness OS. Focal diode laser photocoagula- tears occurred mostly at the margin remains speculative. tion to the point of leakage was per- of the RPE detachment. However, in formed that subsquently resulted in cases of age-related macular degen- Alvin K. H. Kwok, FRCS complete resolution of the exudative eration, the subretinal neovascular Lulu L. Cheng retinaldetachment.Thebest-corrected membrane may exert a tangential Pramod Bhende, MD visual acuity improved to 20/30 OU tractional force on one side of the RPE Dennis S. C. Lam, FRCS, FRCOphth 4 months later. detachment causing an RPE tear at Hong Kong, China Pramod Bhende, MD Tarun Sharma, MD Chennai, India

This investigation was supported in part by the Mr W. K. Lee Eye Foun- dation, Hong Kong, China. We have no proprietary interest in any material relating to this article. Reprints:AlvinK.H.Kwok,FRCS, Department of Ophthalmology and Vi- sual Sciences, The Chinese University of Hong Kong, Prince of Wales Hospi- tal, Shatin, Hong Kong, China (e-mail: [email protected]).

1. Sunakawa M, Tsukahara I. Tear of the retinal pigment epithelium and serous retinal detachment. Am J Ophthalmol. 1985;100:488-489. 2. Friberg TR, Eller AW. Serous retinal detachment resembling central serous chorioretinopathy following organ transplantation. Graefes Arch Clin Exp Ophthalmol. 1990;228:305-309. 3. Krishan NR, Chandra SR, Stevens TS. Diagno- Figure 1. The right fundus photograph shows a large retinal pigment epithelium tear sis and pathogenesis of retinal pigment epithe- along the inferotemporal arcade. lial tear. Am J Ophthalmol. 1985;100:698-707.

Figure 2. Left, Composite photograph of early-phase fluorescein angiography of the right fundus demonstrates a hyperfluorescent lesion representing the denuded Bruch’s membrane. It is lined by 2 almost parallel hypofluorescent bands, which represent the rolled retinal pigment epithelium on each side. Right, A late-phase fluorescein angiogram of the right fundus shows a large hyperfluorescent lesion representing the denuded Bruch’s membrane. It is lined by 2 almost parallel hypofluorescent bands, which represent the rolled retinal pigment epithelium on each side. At the nasal tip of the retinal pigment epithelium tear, a leakage point with profuse leakage is evident.

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