Kevin J. Blinder

Verteporfin therapy of subfoveal choroidal neovascularization in pathologic myopia: 2-Year results of a randomized clinical trial - VIP report no. 3

PURPOSE To report 24-month vision and fluorescein angiographic outcomes from trials evaluating photodynamic therapy with verteporfin in patients with subfoveal choroidal neovascularization (CNV) caused by pathologic myopia. DESIGN AND SETTING Multicenter, double-masked, placebo-controlled, randomized clinical trial at 28 ophthalmology practices in Europe and North America. PARTICIPANTS Patients with subfoveal choroidal neovascular lesions caused by pathologic myopia measuring no more than 5400 micro m and best-corrected visual acuity (approximate Snellen equivalent) of 20/100 or better. METHODS Similar to methods described for 1-year results with follow-up examinations beyond 1 year, continuing every 3 months (except Photograph Reading Center evaluations only at the month 24 examination). During the second year, the same regimen (with verteporfin or placebo as applied at baseline) was used if angiography showed fluorescein leakage from CNV. MAIN OUTCOME MEASURES The primary outcome was the proportion of eyes with fewer than 8 letters (approximately 1.5 lines) of visual acuity loss at the month 24 examination, adhering to an intent-to-treat analysis and using the last observation carried forward method to impute for any missing data. RESULTS Seventy-seven of 81 patients (95%) in the verteporfin group, compared with 36 of 39 patients (92%) in the placebo group, completed the month 24 examination. At this time point, 29 of 81 verteporfin-treated patients (36%) compared with 20 of 39 placebo-treated patients (51%) lost at least 8 letters (P = 0.11). The distribution of change in visual acuity at the month 24 examination was in favor of a benefit for the cases assigned to verteporfin (P = 0.05). This included improvement by at least 5 letters (equivalent to at least 1 line) in 32 verteporfin-treated cases [40%] vs. five placebo-treated cases (13%) and improvement by at least 15 letters (equivalent to at least 3 lines) in 10 verteporfin-treated cases (12%) vs. zero placebo-treated cases. No additional photosensitivity adverse reactions or injection site adverse events were associated with verteporfin therapy in the second year of follow-up. CONCLUSIONS Verteporfin therapy for subfoveal CNV caused by pathologic myopia safely maintained a visual benefit compared with a placebo therapy through 2 years of follow-up. Although the primary outcome was not statistically significantly in favor of verteporfin therapy at 2 years as it had been at 1 year of follow-up, the distribution of change in visual acuity at the month 24 examination was in favor of the verteporfin-treated group and showed that this group was more likely to have improved visual acuity through the month 24 examination. The VIP Study Group recommends verteporfin therapy for subfoveal CNV resulting from pathologic myopia based on both the 1- and 2-year results of this randomized clinical trial.

Effect of lesion size, visual acuity, and lesion composition on visual acuity change with and without verteporfin therapy for choroidal neovascularization secondary to age-related macular degeneration: TAP and VIP report no. 1.

PURPOSE To determine whether differences in baseline lesion size and visual acuity might explain differing results found in three different lesion compositions (predominantly classic, minimally classic, and occult with no classic) among three placebo-controlled, randomized clinical trials evaluating photodynamic therapy with verteporfin (Visudyne, Novartis AG), also termed verteporfin therapy, in patients with subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). METHODS Exploratory analyses were conducted in patients with predominantly classic or minimally classic lesions at enrollment in the Treatment of AMD with Photodynamic Therapy (TAP) Investigation and in AMD patients with occult with no classic CNV in the Verteporfin In Photodynamic Therapy (VIP) Trial. Baseline characteristics of patients among these three lesion compositions were compared. In addition, multiple linear regression modeling was used to explore the effect of baseline lesion size, visual acuity, and lesion composition on mean change in visual acuity from baseline to 24 months. RESULTS At baseline, the mean size of predominantly classic lesions (3.4 disk areas) was smaller than that of minimally classic (4.7 disk areas) and occult with no classic lesions (4.3 disk areas). In the multiple linear regression model of individual lesion compositions, there was a significant treatment-by-lesion-size interaction for minimally classic and occult with no classic lesions, but not for predominantly classic lesions. Interaction between treatment and baseline visual acuity was not significant for any lesion composition. Small verteporfin-treated lesions lost less vision than large verteporfin-treated lesions in each lesion composition. In the multiple linear regression model that included all lesion compositions, lesion size was a more significant predictive factor for the magnitude of treatment benefit than either lesion composition or visual acuity. Smaller (4.0 disk areas or less) minimally classic and occult with no classic lesions had similar visual acuity outcomes to those observed in predominantly classic lesions. CONCLUSIONS Based on exploratory analyses, lesion size in the TAP Investigation and VIP Trial was an important predictor of the magnitude of treatment benefit with verteporfin therapy in occult with no classic and minimally classic lesion compositions. In patients with AMD, treating smaller rather than larger neovascular lesions, regardless of lesion composition, likely will result in a better level of visual acuity.

A Technique for Retinal Pigment Epithelium Transplantation for Age-Related Macular Degeneration Secondary to Extensive Subfoveal Scarring

We describe the surgical excision of submacular scar in end-stage age-related macular degeneration and transplantation of autologous and homologous retinal pigment epithelial (RPE) cells. The technique involves the preparation of a large retinal flap encompassing the macula and the arcades, removal of the submacular scar, and replacement of the RPE cells, using either an autologous pedicle graft or homologous RPE cells and Bruchs membrane. Fourteen months following the procedure, visual acuity in a patient with a pedicle graft had improved from counts fingers to 20/400 and the patient fixated over the transplanted RPE cells. After 10 months, a homologous graft in a second patient had become encapsulated with a fine subretinal membrane without neovascular tissue; visual acuity had not improved. No intraoperative or postoperative complications resulting from the surgery occurred in either patient.

Incidence of endophthalmitis related to intravitreal injection of bevacizumab and ranibizumab.

Purpose: To report the overall incidence of endophthalmitis associated with office based intravitreal injections of bevacizumab and ranibizumab. Methods: This is a retrospective, consecutive, multicenter case series involving four large clinical sites. Included were all patients receiving at least one injection of intravitreal bevacizumab or intravitreal ranibizumab. Follow-up after each injection was at least 4 weeks. Results: A total of 12,585 injections of intravitreal bevacizumab and 14,320 injections of intravitreal ranibizumab were given during the study period. Infectious endophthalmitis developed in three patients after administration of bevacizumab and in three patients after administration of ranibizumab. Four of these patients were culture positive. Rates of endophthalmitis were 0.02% and 0.02%, respectively, with an overall rate of 0.02%. Conclusion: The rate of endophthalmitis associated with intravitreal bevacizumab and ranibizumab is low, with an incidence of approximately 1 in 4,500 injections.

Outcome results in macular hole surgery: An evaluation of internal limiting membrane peeling with and without indocyanine green

PURPOSE To evaluate the anatomic closure rate and visual outcome in patients undergoing pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling with and without indocyanine green (ICG) enhancement. DESIGN Retrospective, noncomparative interventional case series. PARTICIPANTS One hundred ninety-three consecutive patients (204 eyes) seen at the Barnes Retina Institute with the clinical diagnosis of macular hole who underwent PPV between January 1998 and December 2000. INTERVENTION A consecutive series of 97 patients undergoing PPV with or without unilateral epiretinal membrane removal without ILM peeling (group 1), 44 patients with PPV and ILM peeling without ICG (group 2), and 35 patients with ICG-assisted ILM peeling (group 3). RESULTS Overall, 86.4% of the holes closed with one operation, with 75 of 97 (77.3%) eyes in group 1, 43 of 44 (97.7%) eyes in group 2, and 34 of 35 (97.1%) eyes in group 3 (chi(2)= 10.51, P = 0.007). Of the eyes that did not close, 18 patients in group 1 underwent repeat surgery, with 90 of 97 (92.8%) eyes ultimately achieving closure. Visual acuity after surgery was 20/50 or better in 55 of 97 (56.7%) patients, 31 of 44 (70.4%) patients, and 18 of 35 (51.4%) patients in groups 1, 2, and 3, respectively (chi(2) = 3.43, P = 0.18) and increased by 2 or more lines from their preoperative status in 63 of 97 (64.9%) patients, 34 of 44 (77.3%) patients, and 25 of 35 (71.4%) patients, respectively (chi(2)= 2.25, P = 0.32). Multivariate logistic regression demonstrated that use of ILM peeling during vitrectomy increases the chances of developing 20/50 vision or better (odds ratio [OR], 2.4; 95% confidence interval, 1.06-5.45; P = 0.04). No eyes received concurrent cataract extraction with macular hole surgery, but 75 of 166 (45.2%) required cataract extraction postoperatively. Complications included 20 retinal tears, 4 retinal detachments, and 34 patients with postoperative elevations in intraocular pressure (IOP; defined as IOP greater than 30 mmHg). CONCLUSIONS Although this study is limited by the shorter follow-up in patients undergoing ILM peeling with or without ICG relative to the control group, our experience indicates that the use of ILM peeling is associated with a statistically significant improvement in the rate of primary macular hole closure with a single operation.

Combined photodynamic therapy with verteporfin and intravitreal bevacizumab for choroidal neovascularization in age-related macular degeneration.

Purpose: To examine the 7-month results for patients treated with combined photodynamic therapy (PDT) with verteporfin and intravitreal bevacizumab for choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Methods: This is a retrospective series of 24 eyes with juxtafoveal or subfoveal CNV secondary to AMD. Patients were treated with PDT with verteporfin and 1.25 mg of intravitreal bevacizumab. All patients were naive to treatment and had either treatment within a 14-day interval. Main outcome measures were visual acuity stabilization (defined as no change or a gain in visual acuity) and retreatment rate. Results: At the 7-month follow-up, 20 (83%) of 24 patients had stabilization of visual acuity. Sixteen eyes (67%) had improvement in visual acuity. Mean improvement in visual acuity (n = 24) was 2.04 Snellen lines. Fifteen eyes (63%) required only a single combined treatment for CNV resolution. There were no complications, including endophthalmitis, uveitis, and ocular hypertension. Conclusion: The results of this study suggest that combined treatment of PDT with verteporfin and intravitreal bevacizumab may be useful in treating neovascular AMD by reducing retreatment rates and improving visual acuity. Further investigation with large, controlled trials is warranted to outline the appropriate treatment paradigm for combination therapy.

The Management of Giant Retinal Tears Using Perfluoroperhydrophenanthrene: A Multicenter Case Series

OBJECTIVE The purpose of the study was to determine the predictors of success and evaluate the use of perfluoroperhydrophenanthrene as an intraoperative and postoperative tool in the management of giant retinal tears in a multicentered collaborative study. DESIGN Multicentered prospective case series. PARTICIPANTS Twenty-three centers consecutively enrolled 162 eyes of 161 patients with retinal tears 90 degrees or greater in circumferential extent. INTERVENTION Perfluoroperhydrophenanthrene was used as an intraoperative surgical adjunct in all cases and left after surgery in 16 eyes (9.9%). MAIN OUTCOME MEASURES Retinal reattachment and visual acuity. RESULTS Intraoperative reattachment was achieved in 158 eyes (97.5%); 147 eyes (90.7%) remained attached at their most recent follow-up. Seventy-nine eyes (48.8%) experienced an improvement in their visual acuity, 26 eyes (16.0%) remained unchanged, and 57 (35.2%) worsened. Recurrent retinal detachment occurred in 80 patients (49.4%). Other significant postoperative complications included cataract formation in 20 (39.2%) of 51 eyes, macular pucker in 12 (7.4%), corneal decompensation in 10 (6.2%), and hypotony (intraocular pressure equal to or less than 5 mmHg) in 9 (5.6%). A chi-square analysis of preoperative characteristics showed that hypotony (P = 0.007), macular detachment (P = 0.020), a history of cataract extraction (P = 0.003), poor visual acuity (P = 0.000), giant tear extent greater than 180 degrees (P = 0.004), and higher grade proliferative vitreoretinopathy (P = 0.000) all predicted a poor visual outcome. Vitreon (Vitrophage, Inc., Lyons, IL) was left in 16 eyes (9.9%) for an extended postoperative retinal tamponade for between 3 and 1034 days (mean, 87.2 days). The Vitreon was well tolerated, and these eyes experienced a similar outcome and rate of retinal reattachment to the rest of the group. CONCLUSIONS Vitreon is a safe and useful adjunct to pars plana vitrectomy in the management of giant retinal tears and may, additionally, be the perfluorocarbon liquid that can be used most safely as a temporary postoperative tool for extended retinal tamponade, reinforcing its role as a useful adjunct in the management of these complex retinal detachments.

Techniques, rationale, and outcomes of internal limiting membrane peeling

Background: The internal limiting membrane represents the structural interface between the retina and the vitreous and has been postulated to serve several essential functions. Recently, internal limiting membrane peeling has been used in the treatment of a variety of retinal disorders. We review the history, techniques, rationale, and outcomes of internal limiting membrane peeling. Methods: A review of the literature. Results: Internal limiting membrane peeling has been used to successfully treat a variety of retinal disorders including macular hole, epiretinal membrane, diabetic macular edema, retinal vein occlusion, and others. Conclusion: Internal limiting membrane peeling may serve as an important component in the armamentarium of retinal surgery.

Triamcinolone-assisted internal limiting membrane peeling.

Purpose: To review our experience with triamcinolone-assisted pars plana vitrectomy for internal limiting membrane (ILM) peeling for various retinal diseases. Methods: Twenty-one patients underwent surgery in which intraoperative triamcinolone acetonide (TA) was used. Indications for surgery included epiretinal membrane (3 patients), branch retinal vein occlusion associated with macular edema (2), traction retinal detachment (3), diabetic macular edema (4), vitreous hemorrhage with diabetic macular edema (4), macular hole (4), and cystoid macular edema (1). Results: TA was useful in the removal of the ILM in all cases. There were no intraoperative complications or toxicity. The mean follow-up was 22 weeks (range, 9–30 weeks). Eleven patients improved by ≥2 Snellen lines, 1 lost ≥2 Snellen lines, and 9 were within 2 Snellen lines of preoperative vision at the last follow-up. Conclusions: The intraoperative use of TA improves visualization of ILMs associated with a variety of conditions. No intraoperative or postoperative complications were observed. TA-assisted removal of the ILM appears to be safe and cost effective. TA-assisted ILM peeling should be considered as an alternative to the use of intraoperative dyes.

Malignant transformation of an optic disk melanocytoma

PURPOSE To report a case of malignant transformation of an optic disk melanocytoma with a second melanocytoma in the ciliary body. METHODS Clinical data including visual acuity, visual fields, color fundus photographs, fluorescein angiogram, and ultrasonogram and histopathologic studies of this case were reviewed. RESULTS The right eye of a 65-year-old white woman was diagnosed with melanocytoma of the optic nerve. Four years later, the tumor became significantly larger. The best-corrected visual acuity declined from 20/40 to counting fingers and the size of the tumor increased fourfold in 2 years. The right globe was enucleated. Histopathologic studies demonstrated moderately pigmented spindle-B malignant melanoma cells adjacent to and within a population of large, polyhedral, heavily pigmented melanocytoma cells that extended to the lamina cribrosa and optic nerve. There was also a deeply pigmented melanocytoma in the ciliary body. CONCLUSION This is a rare case of malignant melanoma transformed from an optic disk melanocytoma. Periodic follow-up of the patient with optic disk melanocytoma is necessary.