Purpose: To evaluate the efficacy of subconjunctival carboplatin in fibrin sealant in the treatment of transgenic murine retinoblastoma.Design: Experimental study using LH beta-Tag transgenic mice in a randomized controlled trial.Participants and Controls: Thirty-three 10-week-old LH beta-Tag transgenic mice: 22 carboplatin-treated animals and 11 control animals.Methods: Three groups of 11 mice were treated with a single, 30 mu l injection of fibrin sealant in the subconjunctival space of 1 eye; the opposite eye was left untreated as an internal control. Group 1 (low-dose group) received 37.5 mg/ml calculated concentration of carboplatin in fibrin sealant (0.66 mg measured total dose). Group 2 (high-dose group) received 75 mg/ml calculated concentration of carboplatin in fibrin sealant (1.23 mg measured total dose). Group 3 (control group) received fibrin sealant only. Mice were killed on day 22 after treatment. Eyes were serially sectioned, and retinal tumor burden was quantified by histopathologic analysis. For statistical analysis of treatment effects, eyes were divided into 6 groups: low-dose group, sealant-treated eyes; low-dose group, untreated eyes; high-dose group, sealant-treated eyes; high-dose group, untreated eyes; control group, sealant-treated eyes; and control group, untreated eyes.Main Outcome Measures: Main outcome measure was mean tumor burden per level per eye in each experimental group.Results: The best therapeutic results were obtained in eyes treated with low-dose carboplatin in fibrin sealant, where no histopathologic evidence of toxicity was observed, and 6 of 11 eyes had zero tumor burden. Tumor burden in the remaining 5 eyes in this group was minimal (4 eyes) or moderate (11 eye) compared with mean control values. Mean tumor burden in this group was significantly smaller than mean tumor burden in untreated eyes from the same mice (P<0.004), sealant-treated eyes in the control group (P<0.004), and untreated eyes in the control group (P<0.002). Although a similar reduction in mean tumor burden was observed in eyes treated with high-dose carboplatin in fibrin sealant, 5 of 10 eyes analyzed in this group also demonstrated histopathologic evidence of severe toxicity.Conclusions: Subconjunctival carboplatin in fibrin sealant is effective in the treatment of transgenic murine retinoblastoma. A single injection of low-dose carboplatin in fibrin sealant was sufficient to induce complete or near-complete intraocular tumor regression in 10 of 11 eyes (91%), with no associated histologic evidence of toxicity. These results suggest that subconjunctival carboplatin in fibrin sealant provides sustained release and could have clinical use in the treatment of intraocular retinoblastoma.

Objective: To evaluate the safety, effect on visual function, and fluorescein angiographic appearance of subfoveal choroidal neovascularization (CNV) through 2 years after photodynamic therapy with verteporfin (Visudyne; Novartis AG, Basel, Switzerland) in patients with ocular histoplasmosis syndrome (OHS).Design: Open-label, 3-center, uncontrolled clinical study.Participants: Ocular histoplasmosis syndrome patients with subfoveal CNV (N = 26) with a greatest linear dimension no larger than 5400 gm with classic or occult CNV extending under the geometric center of the fovea, and best-corrected visual acuity letter score of approximately 20/40 to 20/200.Methods: The methods were similar to those described in the 1-year results with follow-up examinations every 3 months continuing through the second year. During the second year, additional therapy was recommended if fluorescein angiography showed leakage at a scheduled visit.Main Outcome Measurements: Visual function measurements included the changes from baseline in visual acuity and contrast sensitivity scores. Lesion size and leakage from classic and occult CNV were assessed at month 12 and month 24. Safety assessments also were made.Results: A 24-month examination was completed in 22 of the 26 enrolled participants (85%). At the 24-month examination, median improvement from baseline in visual acuity of the 22 patients evaluated was 6 letters; median contrast sensitivity improved by 3.5 letters. At the 24-month examination, 10 patients (45%) gained 7 or more letters of visual acuity from baseline, whereas 4 patients (18%) lost 8 or more letters, including 2 patients (9%) who lost at least 15 letters. There was absence of fluorescein angiographic leakage from classic CNV in 17 of the 20 evaluable lesions (85%), and leakage from occult CNV was absent in all eyes. No serious ocular adverse events were reported, and no serious systemic event was considered to be associated with treatment.Conclusions: Median visual acuity improved and fluorescein angiographic leakage decreased after verteporfin therapy in this small, uncontrolled clinical study of patients with subfoveal CNV resulting from OHS. Verteporfin therapy seemed to be relatively safe in these patients. The selected cases feature fluorescein angiographic examples of CNV that are important in determining when to apply verteporfin therapy. (C) 2004 by the American Academy of Ophthalmology.

We have read with interest the article by Zaldivar and associates that appeared in the May 2003 issue of the American Journal of Ophthalmology (Am J Ophthalmol 2003;135:657–663). The authors have reviewed the clinicopathologic features of eyes enucleated after failed transpupillary thermotherapy (TTT). They have brought out an interesting point that choroidal melanomas may continue to grow along the path of least resistance even after TTT and, thus, manifest recurrences. The presence of intrascleral melanoma cells has been cited as the cause of tumor recurrence after TTT. 1 Korver J. Keunen J. Thermotherapy in the management of choroidal melanoma. Prog Retin Eye Res. 2002; 21: 303-317 Crossref PubMed Scopus (33) Google Scholar Author replyAmerican Journal of OphthalmologyVol. 137Issue 3Preview Full-Text PDF

OBJECTIVE To assess the association of ocular disorders and high doses of antioxidants or zinc with mortality in the Age-Related Eye Disease Study (AREDS). METHODS Baseline fundus and lens photographs were used to grade the macular and lens status of AREDS participants. Participants were randomly assigned to receive oral supplements of high-dose antioxidants, zinc, antioxidants plus zinc, or placebo. Risk of all-cause and cause-specific mortality was assessed using adjusted Cox proportional hazards models. RESULTS During median follow-up of 6.5 years, 534 (11%) of 4753 AREDS participants died. In fully adjusted models, participants with advanced age-related macular degeneration (AMD) compared with participants with few, if any, drusen had increased mortality (relative risk [RR], 1.41; 95% confidence interval [CI], 1.08-1.86). Advanced AMD was associated with cardiovascular deaths. Compared with participants having good acuity in both eyes, those with visual acuity worse than 20/40 in 1 eye had increased mortality (RR, 1.36; 95% CI, 1.12-1.65). Nuclear opacity (RR, 1.40; 95% CI, 1.12-1.75) and cataract surgery (RR, 1.55; 95% CI, 1.18-2.05) were associated with increased all-cause mortality and with cancer deaths. Participants randomly assigned to receive zinc had lower mortality than those not taking zinc (RR, 0.73; 95% CI, 0.61-0.89). CONCLUSIONS The decreased survival of AREDS participants with AMD and cataract suggests that these conditions may reflect systemic rather than only local processes. The improved survival in individuals randomly assigned to receive zinc requires further study.

Purpose: To update the findings from the Choroidal Neovascularization Prevention Trial (CNVPT) with respect to resolution of drusen, incidence of choroidal neovascularization, and visual function.Design: A multicenter, randomized, controlled, pilot clinical trial.Participants: The 120 patients enrolled in the CNVPT. Patients had signs of choroidal neovascularization or retinal pigment epithelial detachment in 1 eye and had less than or equal to10 large (>63-mum) drusen in the contralateral, or fellow, eye.Intervention: The fellow eye of 59 patients was assigned randomly to argon green laser treatment consisting of multiple 100-mum spots at least 750 mum from the center of the fovea. The fellow eye of the remaining 61 patients was assigned randomly to observation.Main Outcome Measures: Change in visual acuity was the primary outcome measure. Incidence of choroidal neovascularization, resolution of drusen, change in contrast threshold, change in critical print size for reading, and incidence of geographic atrophy were secondary outcome measures.Results: Throughout 4 years of follow-up, there were no statistically significant differences in change in visual acuity, contrast threshold, critical print size, or incidence of geographic atrophy. With additional follow-up, the large increase in the incidence of choroidal neovascularization observed within 18 months of treatment was maintained; however, by 30 months, the incidence in the two treatment groups was the same. Most drusen resolution in treated eyes occurred within 24 months of the initial treatment. Treated eyes that received higher-intensity laser burns had an increased risk of choroidal neovascularization. Among eyes developing choroidal neovascularization in each treatment group, most lesions (two thirds or more) were composed of occult neovascularization only.Conclusions: Laser treatment as applied in the CNVPT caused an excess risk of choroidal neovascularization in the first year or so after treatment. The increased early incidence of choroidal neovascularization was not associated with either a harmful or beneficial effect in this pilot study.

PURPOSE:To describe two patients with unique lenticular nodular proliferations. DESIGN:Observational case reports. METHODS:The clinical histories and pathologic findings of two patients with lenticular nodular proliferations were reviewed. RESULTS:One patient with persistent hyperplastic primary vitreous and another patient with trauma developed lenticular nodular proliferations. The nodules were vascularized collections of foamy histiocytes, multinucleated cells, lens capsule, and lens epithelium that had undergone fibrous metaplasia. The lesions were classified as lenticular fibroxanthomatous nodules. CONCLUSIONS:A lenticular fibroxanthomatous nodule is a unique clinicopathologic entity that should be differentiated from Soemmerring ring, Elschnig pearl, and other simulating entities such as juvenile xanthogranuloma.

This study determined the in vitro permeability of cisplatin through isolated human sclera as delivered by a collagen matrix vehicle. Short-term and long-term intraocular levels of cisplatin were also measured in the rabbit eye after a subconjunctival injection. Cisplatin in either a collagen matrix vehicle or a control balanced salt solution (BSS) vehicle was applied to human sclera mounted in a specially designed in vitro perfusion chamber. The amount of cisplatin that diffused across the sclera was measured in hourly samples for 24 h using atomic absorption spectrometry. In vivo studies were also performed in Dutch Belted rabbits given subconjunctival injections of cisplatin in collagen matrix or in BSS. Eyes were enucleated at 1.5 h and 2 weeks after injection, frozen, and dissected to determine the intraocular cisplatin concentrations. Cisplatin had a peak in vitro scleral permeability constant of 8.3+/-1.2 x 10(-6) and 20.1+/-1.8 x 10(-6) cm/s, delivered in collagen matrix and in BSS, respectively (mean+/-S.D.). At the end of the in vitro experiments, 35.9+/-4.6% of the cisplatin remained in the collagen matrix, while 0.8+/-0.2% remained in the BSS vehicle. Subconjunctival injection of cisplatin in the collagen matrix vehicle achieved 3.3+/-0.1 microg/ml in the vitreous humor at 1.5 h and 0.1+/-0.1 microg/ml at 2 weeks. This vehicle also achieved a cisplatin concentration of 73.5+/-23.9 microg/mg in the choroid and retina at 1.5 h and 3.2+/-1.3 microg/mg at 2 weeks. Compared to BSS, the collagen matrix vehicle provided a more controlled release of cisplatin, and after subconjunctival injection into rabbits, attained higher drug levels in several ocular tissues.

PURPOSE:To report the results of macular hole surgery using indocyanine green to improve visualization and facilitate peeling of the internal limiting membrane. METHODS:A retrospective noncomparative review of a consecutive series of 22 patients (22 eyes) who underwent macular hole repair using indocyanine green to facilitate visualization of the internal limiting membrane was performed. One patient was excluded because of a history of a rhegmatogenous retinal detachment. All patients underwent a three-port pars plana vitrectomy with internal limiting membrane peeling. Indocyanine green (0.1% solution) was used to assist in the visualization of the internal limiting membrane. The main outcome measures were postoperative visual acuity, macular hole status, and postoperative retinal pigment epithelial changes. RESULTS:In 21 eyes, the median preoperative best-corrected visual acuity was 20/200 (range, 20/60 to counting fingers at 5 feet). The median postoperative visual acuity was 20/400 (range, 20/60-1/200) with an average follow-up of 13 weeks. The macular hole was closed in 18 eyes (86%) at the most recent follow-up. Ten eyes were found to have atrophic retinal pigment epithelium changes in the area of the previous macular hole. CONCLUSIONS:Indocyanine green assists in visualization of the internal limiting membrane in macular hole surgery. In our series, 10 eyes had unusual atrophic changes in the retinal pigment epithelium at the site of the previous macular hole, or in the area where the indocyanine green solution would have had direct access to the bare retinal pigment epithelium cells. Although the use of indocyanine green improves visualization and assists with peeling of the internal limiting membrane, the safety and potential toxicity of indocyanine green to the retinal pigment epithelium require further investigation.

Purpose: During the past decade, laser photoablation has supplanted cryotherapy as the standard treatment for threshold retinopathy of prematurity (ROP). We evaluated the progression and the complication rate in a cohort of infants with threshold ROP treated with a confluent technique. Methods:We retrospectively studied 47 patients with ROP (91 eyes), treated with confluent diode laser photoablation. Four main outcomes were evaluated: (1) the rate of progression, (2) the frequency of laser retreatment, (3) postoperative complications, and (4) postoperative refractive error. Results: A mean of 1943 +/- 912 laser burns were administered in a confluent pattern to 91 eyes with threshold ROP. Progression to stage 4 or 5 disease occurred in 13 of 29 eyes (44.8%) with zone I and posterior zone II and in 2 of 51 eyes (3.9%) with anterior zone II ROP (P = .01). Eyes with anterior zone II ROP that received more than or equal to 2000 burns progressed more than those that received fewer than 2000 burns. Only 1 eye (1%) needed a supplemental laser treatment. Postoperative complications included corneal edema (2.3%), anterior segment ischemia (2.3%), vitreous hemorrhage (7.9%), posterior synechiae (2.3%), cataract (4.9%), and macular ectopia (12%). The mean spherical equivalent at the last follow-up was -4.52 +/- 5.63 D. Conclusions: In our series, infants received more laser burns than infants reported in the literature receiving scatter or near-confluent treatment. While confluent treatment almost eliminated supplemental treatment, it was associated with a similar rate of progression and complications as has been reported with other patterns of laser treatment.

OBJECTIVETo report the visual outcome in patients with a neovascular membrane (NVM) associated with idiopathic juxtafoveolar telangiectasis (IJFT).METHODSWe performed a retrospective, noncomparative analysis of 26 eyes of 16 patients with an NVM associated with bilateral IJFT (Gass classification group 2A). Eyes were divided into 2 groups: group WO (n = 11) included eyes with IJFT without evidence of an NVM on initial examination; eyes in group W (n = 15) had an NVM at the initial diagnosis of IJFT. In group WO, the initial visual acuity and the time between the initial examination to the diagnosis of an NVM were evaluated. Characteristic fundus findings, including the presence or absence of a chorioretinal anastomosis, intraretinal pigmentary plaques, and crystalline deposits, as well as the final visual acuity were reviewed for both groups.RESULTSThe initial visual acuity for eyes in group WO ranged from 20/20 to 20/70 (median, 20/30); in group W, from 20/20 to 4/200 (median, 20/70). The average time from initial diagnosis of IJFT to the development of an NVM was 73 months (range, 5-142 months). In group WO, chorioretinal anastomosis and concurrent perivascular retinal pigment epithelial hyperplasia were observed before the development of an NVM. The final visual acuity for all eyes ranged from 20/40 to 2/200 (median, 20/200). Eighty-one percent of eyes (21/26) had a final visual acuity of 20/200 or worse.CONCLUSIONSThe stable final visual acuity in patients with an NVM associated with IJFT is generally poor, with 80% of eyes in this series having a final visual acuity of l20/200 or worse. In patients with IJFT, the presence of a chorioretinal anastomosis and retinal pigment epithelial hyperplastic plaques always preceded the development of an NVM.