Complement C3 Inhibitor Pegcetacoplan for Geographic Atrophy Secondary to Age-Related Macular Degeneration: A Randomized Phase 2 Trial.

PURPOSE: Geographic atrophy (GA), a late stage of age-related macular degeneration (AMD), is a major cause of blindness. Even while central visual acuity remains relatively well preserved, GA often causes considerable compromise of visual function and quality of life. No treatment currently exists. We evaluated the safety and efficacy of pegcetacoplan, a complement C3 inhibitor, for treatment of GA. DESIGN: Prospective, multicenter, randomized, sham-controlled phase 2 study. PARTICIPANTS: Two hundred forty-six patients with GA. METHODS: Patients with GA were assigned randomly in a 2:2:1:1 ratio to receive intravitreal injections of 15 mg pegcetacoplan monthly or every other month (EOM) or sham intravitreal injections monthly or EOM for 12 months with follow-up at months 15 and 18. Area and growth of GA were measured using fundus autofluorescence imaging. MAIN OUTCOME MEASURES: The primary efficacy end point was mean change in square root GA lesion area from baseline to month 12. Secondary outcome measures included mean change from baseline in GA lesion area without the square root transformation, distance of GA lesion from the fovea, best-corrected visual acuity (BCVA), low-luminance BCVA, and low-luminance visual acuity deficit. The primary safety end point was the number and severity of treatment-emergent adverse events. RESULTS: In patients receiving pegcetacoplan monthly or EOM, the GA growth rate was reduced by 29% (95% confidence interval [CI], 9-49; P = 0.008) and 20% (95% CI, 0-40; P = 0.067) compared with the sham treatment group. Post hoc analysis showed that the effect was greater in the second 6 months of treatment, with observed reductions of 45% (P = 0.0004) and 33% (P = 0.009) for pegcetacoplan monthly and EOM, respectively. Two cases of culture-positive endophthalmitis and 1 case of culture-negative endophthalmitis occurred in the pegcetacoplan monthly group. New-onset investigator-determined exudative AMD was reported more frequently in pegcetacoplan-treated eyes (18/86 eyes [20.9%] and 7/79 eyes [8.9%] in monthly and EOM groups, respectively) than in sham-treated eyes (1/81 eyes [1.2%]). CONCLUSIONS: Local C3 inhibition with pegcetacoplan resulted in statistically significant reductions in the growth of GA compared with sham treatment. Phase 3 studies will define the efficacy and safety profile further.

Consensus Nomenclature for Reporting Neovascular Age-Related Macular Degeneration Data: Consensus on Neovascular Age-Related Macular Degeneration Nomenclature Study Group.

PURPOSE: To establish a process to evaluate and standardize a state-of-the-art nomenclature for reporting neovascular age-related macular degeneration (AMD) data. DESIGN: Consensus meeting. PARTICIPANTS: An international panel of retina specialists, imaging and image reading center experts, and ocular pathologists. METHODS: During several meetings organized under the auspices of the Macula Society, an international study group discussed and codified a set nomenclature framework for classifying the subtypes of neovascular AMD and associated lesion components. MAIN OUTCOME MEASURES: A consensus classification of neovascular AMD. RESULTS: The study group created a standardized working definition of AMD. The components of neovascular AMD were defined and subclassified. Disease consequences of macular neovascularization were delineated. CONCLUSIONS: The framework of a consensus nomenclature system, a definition of AMD, and a delineation of the subtypes of neovascular AMD were developed. Establishing a uniform set of definitions will facilitate comparison of diverse patient groups and different studies. The framework presented is modified and updated readily, processes that are anticipated to occur on a periodic basis. The study group suggests that the consensus standards outlined in this article be used in future reported studies of neovascular AMD and clinical practice.

Effect of Ciliary Neurotrophic Factor on Retinal Neurodegeneration in Patients with Macular Telangiectasia Type 2: A Randomized Clinical Trial.

PURPOSE: To test the effects of an encapsulated cell-based delivery of a neuroprotective agent, ciliary neurotrophic factor (CNTF), on progression of macular telangiectasia type 2, a neurodegenerative disease with no proven effective therapy. DESIGN: Randomized sham-controlled clinical trial. PARTICIPANTS: Ninety-nine study eyes of 67 eligible participants were enrolled. METHODS: Single-masked randomized clinical trial of 24 months' duration conducted from May 2014 through April 2017 in 11 clinical centers of retinal specialists in the United States and Australia. Participants were randomized 1:1 to surgical implantation of intravitreal sustained delivery of human CNTF versus a sham procedure. MAIN OUTCOME MEASURES: The primary outcome was the difference in the area of neurodegeneration as measured in the area of the ellipsoid zone disruption (or photoreceptor loss) measured on spectral-domain (SD) OCT images at 24 months from baseline between the treated and untreated groups. Secondary outcomes included comparison of visual function changes between treatment groups. RESULTS: Among the 67 participants who were randomized (mean age, 62±8.9 years; 41 women [61%]; 58 white persons [86%]), 65 (97%) completed the study. Two participants (3 study eyes) died and 3 participants (4 eyes) were found ineligible. The eyes receiving sham treatment had 31% greater progression of neurodegeneration than the CNTF-treated eyes. The difference in mean area of photoreceptor loss was 0.05±0.03 mm2 (P = 0.04) at 24 months. Retinal sensitivity changes, measured using microperimetry, were correlated highly with the changes in the area of photoreceptor loss (r = 0.86; P < 0.0001). The mean retinal sensitivity loss of the sham group was 45% greater than that of the treated group (decrease, 15.81±8.93 dB; P = 0.07). Reading speed deteriorated in the sham group (-13.9 words per minute) with no loss in the treated group (P = 0.02). Serious adverse ocular effects were found in 2 of 51 persons (4%) in the sham group and 2 of 48 persons (4%) in the treated group. CONCLUSIONS: In participants with macular telangiectasia type 2, a surgical implant that released CNTF into the vitreous cavity, compared with a sham procedure, slowed the progression of retinal degeneration. Further research is needed to assess longer-term clinical outcomes and safety.

Brolucizumab Versus Aflibercept in Participants with Neovascular Age-Related Macular Degeneration: A Randomized Trial.

PURPOSE: To compare the efficacy and safety of brolucizumab with aflibercept to treat neovascular age-related macular degeneration (AMD). DESIGN: Prospective, randomized, double-masked, multicenter, 2-arm, phase 2 study. PARTICIPANTS: Eighty-nine treatment-naïve participants, aged ≥50 years, with active choroidal neovascularization secondary to AMD. METHODS: Eligible participants were randomized 1:1 to intravitreal brolucizumab (6 mg/50 µl) or aflibercept (2 mg/50 µl). Both groups received 3 monthly loading doses and were then treated every 8 weeks (q8) with assessment up to week 40. In the brolucizumab group, the final q8 cycle was extended to enable 2 cycles of treatment every 12 weeks (q12; to week 56); participants on aflibercept continued on q8. Unscheduled treatments were allowed at the investigator's discretion. MAIN OUTCOME MEASURES: The primary and secondary hypotheses were noninferiority (margin: 5 letters at a 1-sided alpha level 0.1) in best-corrected visual acuity (BCVA) change from baseline of brolucizumab versus aflibercept at weeks 12 and 16, respectively. BCVA, central subfield thickness (CSFT), and morphologic features were assessed throughout the study. RESULTS: The mean BCVA change from baseline (letters) with brolucizumab was noninferior to aflibercept at week 12 (5.75 and 6.89, respectively [80% confidence interval for treatment difference, -4.19 to 1.93]) and week 16 (6.04 and 6.62 [-3.72 to 2.56]), with no notable differences up to week 40. Outcomes exploring disease activity during the q8 treatment cycles suggest greater stability of the brolucizumab participants, supported by receipt of fewer unscheduled treatments versus aflibercept (6 vs. 15) and more stable CSFT reductions. In addition, from post hoc analysis, a greater proportion of brolucizumab-treated eyes had resolved intraretinal and subretinal fluid compared with aflibercept-treated eyes. Approximately 50% of brolucizumab-treated eyes had stable BCVA during the q12 cycles. Brolucizumab and aflibercept adverse events were comparable. CONCLUSIONS: During the matched q8 phase, the BCVA in brolucizumab-treated eyes appeared comparable to aflibercept-treated eyes, with more stable CSFT reductions, receipt of fewer unscheduled treatments, and higher rates of fluid resolution. The brolucizumab safety profile was similar to aflibercept over 56 weeks of treatment. A 12-week treatment cycle for brolucizumab may be viable in a relevant proportion of eyes.

Investigation of oral fenretinide for treatment of geographic atrophy in age-related macular degeneration.

BACKGROUND: Excessive accumulation of retinol-based toxins has been implicated in the pathogenesis of geographic atrophy (GA). Fenretinide, an orally available drug that reduces retinol delivery to the eye through antagonism of serum retinol-binding protein (RBP), was used in a 2-year trial to determine whether retinol reduction would be effective in the management of geographic atrophy. METHODS: The efficacy of fenretinide (100 and 300 mg daily, orally) to slow lesion growth in geographic atrophy patients was examined in a 2-year, placebo-controlled double-masked trial that enrolled 246 patients at 30 clinical sites in the United States. RESULTS: Fenretinide treatment produced dose-dependent reversible reductions in serum RBP-retinol that were associated with trends in reduced lesion growth rates. Patients in the 300 mg group who achieved serum retinol levels of ≤ 1 µM (≤ 2 mg/dL RBP) showed a mean reduction of 0.33 mm in the yearly lesion growth rate compared with subjects in the placebo group (1.70 mm/year vs. 2.03 mm/year, respectively, P = 0.1848). Retinol-binding protein reductions <2 mg/dL correlated with further reductions in lesion growth rates (r = 0.478). Fenretinide treatment also reduced the incidence of choroidal neovascularization (approximately 45% reduction in incidence rate in the combined fenretinide groups vs. placebo, P = 0.0606). This therapeutic effect was not dose dependent and is consistent with anti-angiogenic properties of fenretinide, which have been observed in other disease states. CONCLUSION: The findings of this study and the established safety profile of fenretinide in chronic dosing regimens warrant further study of fenretinide in the treatment of geographic atrophy.

Switching to brolucizumab: injection intervals and visual, anatomical and safety outcomes at 12 and 18 months in real-world eyes with neovascular age-related macular degeneration.

BACKGROUND: The anti-vascular endothelial growth factor (anti-VEGF) injection interval influences treatment burden and compliance in neovascular age-related macular degeneration (nAMD). This real-world study investigates visual acuity (VA), injection-interval extension, central macular thickness (CMT) and safety in nAMD eyes switched to the anti-VEGF agent brolucizumab and followed for up to 18 months. METHODS: This retrospective study included patients with nAMD who were switched from other anti-VEGF agents to brolucizumab only. Patient eyes were grouped into three nested cohorts with the overall cohort receiving ≥ 1 brolucizumab injection, the second receiving ≥ 3 brolucizumab injections with a follow-up period of ≥ 12 months and the third cohort receiving ≥ 3 brolucizumab injections with a follow-up period of ≥ 18 months. Study endpoints included changes from baseline at 12 or 18 months in VA, injection intervals, and CMT. Sub-group analyses were conducted using baseline injection interval length or baseline VA as qualifiers. RESULTS: Overall, 482 eyes received ≥ 1 brolucizumab injection; 174 eyes received ≥ 3 brolucizumab injections with ≥ 12 months of follow-up, and 95 eyes received ≥ 3 brolucizumab injections with ≥ 18 months of follow-up. VA (mean [95% confidence intervals]) remained stable relative to baseline after 12 months (- 1.1 [- 3.7, 1.6] letters; p = 0.42) and 18 months (0.0 [- 3.1, 3.1] letters; p = 0.98) of brolucizumab treatment, respectively, and pre-switch injection intervals or baseline VA had no notable effect. Following the switch to brolucizumab, injection intervals were extended from baseline to month 12 by 26.9 (19.7, 34.0) days (p < 0.0001), and eyes with pre-switch injection intervals < 8 weeks were able to have their injection intervals extended by 23.6 days longer than eyes with pre-switch injection intervals ≥ 8 weeks. At 18 months, injection intervals were extended by 36.3 (25.6, 46.9) days (p < 0.0001) compared to baseline. Following switch to brolucizumab, CMT was reduced at both 12 and 18 months (12 months: - 35.2 (- 51.7, - 18.8) µm, p < 0.0001; 18 months: - 38.9 (- 54.3, - 22.0) µm, p < 0.0001). Intraocular inflammation-related adverse events were reported in 4.6% of brolucizumab-treated eyes. CONCLUSIONS: This real-world study demonstrates that injection intervals may be significantly extended with maintained vision and reduced CMT in nAMD eyes switching to brolucizumab therapy from other anti-VEGFs.

One-Year and 18-Month Outcomes in nAMD Patient Eyes Switched to Brolucizumab Alone versus to Brolucizumab Alternating with Other Anti-VEGF Agents.

Objective: Retrospective, real-world study to evaluate visual acuity (VA), anti-vascular endothelial growth factor (anti-VEGF) injection intervals, and central macular thickness (CMT) in neovascular age-related macular degeneration (nAMD) eyes switched to brolucizumab only or to brolucizumab alternating with another anti-VEGF. Methods: The overall study population comprised eyes that were given ≥1 brolucizumab injection between 1 October 2019 and 30 November 2021. The brolucizumab-only (BRO) cohort consisted of prior anti-VEGF-treated eyes treated exclusively with ≥3 brolucizumab injections over ≥12 or ≥18 months; the alternating brolucizumab (ALT) cohort comprised prior anti-VEGF-treated eyes treated with ≥2 brolucizumab injections and ≥1 other anti-VEGF over ≥12 or ≥18 months. Results: A total of 482 eyes received ≥1 brolucizumab injection during the study period. Mean VA changes from baseline were -1.1±15.1 letters (BRO cohort; n = 174) and 1.3±13.0 letters (ALT cohort; n = 47) at Month 12, and 0.0±13.5 letters (BRO cohort; n = 95) and -7.3±17.2 letters (ALT cohort; n = 29) at Month 18. Mean changes in injection intervals were +26.9±48.1 days (BRO cohort) and +11.1±17.3 days (ALT cohort) at Month 12 and +36.3±52.3 days (BRO cohort) and +14.0±19.9 days (ALT cohort) at Month 18. Mean changes in CMT were -35.2±108.1 µm (BRO cohort) and -31.5±91.2 µm (ALT cohort) at Month 12 and -38.9±75.0 µm (BRO cohort) and -9.0±59.9 µm (ALT cohort) at Month 18. Intraocular inflammation-related adverse events were recorded in 22/482 (4.6%) eyes. Conclusion: Treatment with either brolucizumab alone or brolucizumab alternating with another anti-VEGF can preserve vision, reduce CMT, and extend anti-VEGF injection intervals in patients with nAMD.

Detection of new-onset choroidal neovascularization using optical coherence tomography: the AMD DOC Study.

PURPOSE: To determine the sensitivity of time domain optical coherence tomography (OCT) in detecting conversion to neovascular age-related macular degeneration (AMD) in eyes at high risk for choroidal neovascularization (CNV), compared with detection using fluorescein angiography (FA) as the gold standard. DESIGN: Prospective, multicenter, observational study. PARTICIPANTS: Individuals aged ≥50 years with nonneovascular AMD at high risk of progressing to CNV in the study eye and evidence of neovascular AMD in the fellow eye. METHODS: At study entry and every 3 months through 2 years, participants underwent best-corrected visual acuity, supervised Amsler grid testing, preferential hyperacuity perimetry (PHP) testing, stereoscopic digital fundus photographs with FA, and OCT imaging. A central Reading Center graded all images. MAIN OUTCOMES MEASURES: The sensitivity of OCT in detecting conversion to neovascular AMD by 2 years, using FA as the reference standard. Secondary outcomes included comparison of sensitivity, specificity, positive predictive value, and negative predictive value of OCT, PHP, and supervised Amsler grid relative to FA for detecting incident CNV. RESULTS: A total of 98 participants were enrolled; 87 (89%) of these individuals either completed the 24-month visit or exited the study after developing CNV. Fifteen (17%) study eyes had incident CNV confirmed on FA by the Reading Center. The sensitivity of each modality for detecting CNV was: OCT 0.40 (95% confidence interval [CI], 0.16-0.68), supervised Amsler grid 0.42 (95% CI, 0.15-0.72), and PHP 0.50 (95% CI, 0.23-0.77). Treatment for incident CNV was recommended by the study investigator in 13 study eyes. Sensitivity of the testing modalities for detection of CNV in these 13 eyes was 0.69 (95% CI, 0.39-0.91) for OCT, 0.50 (95% CI, 0.19-0.81) for supervised Amsler grid, and 0.70 (95% CI, 0.35-0.93) for PHP. Specificity of the OCT was higher than that of the Amsler grid and PHP. CONCLUSIONS: Time-domain OCT, supervised Amsler grid, and PHP have low to moderate sensitivity for detection of new-onset CNV compared with FA. Optical coherence tomography has greater specificity than Amsler grid or PHP. Among fellow eyes of individuals with unilateral CNV, FA remains the best method to detect new-onset CNV.

A Smart Mobile Application to Monitor Visual Function in Diabetic Retinopathy and Age-Related Macular Degeneration: The CLEAR Study.

PURPOSE: The purpose of this study was to determine if a mobile application, the Checkup Vision Assessment System, could reliably monitor visual acuity (VA) and metamorphopsia remotely versus standard VA reference tests in the clinic. With the current COVID-19 pandemic, an even greater need for remote monitoring exists. Mobile tools enhance the ability to monitor patients virtually by enabling remote monitoring of VA and Amsler grid findings. DESIGN: Prospective, multicenter reliability analysis. METHODS: Participants: Patients (N = 108) with near corrected VA better than 20/200 and a diagnosis of age-related macular degeneration, diabetic retinopathy, or healthy patients without retinal disease (best-corrected visual acuity [BCVA] of 20/32 or better). INTERVENTION: participants were tested using the Checkup, reference VA, and Amsler tests, with the order of testing (Checkup or reference) randomized. Patients monitored their vision using Checkup at least twice a week at home between office visits. Main outcome measurements were near corrected VA and Amsler grid test results. RESULTS: Agreement was strong between Checkup and reference tests for VA (r = 0.86) and Amsler grid (sensitivity: 93%; specificity: 92%). Home versus clinic testing showed excellent agreement (r = 0.96). Patients reported successful home use. There were no serious adverse events or discontinuations. Patients rated the usability of Checkup to be excellent. CONCLUSIONS: There was good agreement between Checkup and in-clinic test results for VA and Amsler grid. The low variance of Checkup testing, agreement between in-clinic and home results, and excellent usability support Checkup as a reliable method for monitoring retinal pathology in clinic and home settings.

Combination therapy using the small interfering RNA bevasiranib.

Bevasiranib, the first small interfering RNA agent developed for the treatment of neovascular age-related macular degeneration, has demonstrated clinical promise. Injected intravitreally, this small interfering RNA acts by inducing catalytic destruction of messenger RNA to silence gene expression. Bevasiranib targets the production of vascular endothelial growth factor (VEGF) protein. It does not affect existing VEGF protein, suggesting that it may offer a synergistic effect when given in combination with anti-VEGF treatments, such as ranibizumab. The safety of bevasiranib has been supported by preclinical and clinical research.

A phase II randomized clinical trial of intravitreal bevacizumab for diabetic macular edema.

OBJECTIVE: To provide data on the short-term effect of intravitreal bevacizumab for diabetic macular edema (DME). DESIGN: Randomized phase II clinical trial. PARTICIPANTS: One hundred twenty-one eyes of 121 subjects (109 eligible for analysis) with DME and Snellen acuity equivalent ranging from 20/32 to 20/320. INTERVENTIONS: Random assignment to 1 of 5 groups: (A) focal photocoagulation at baseline (n = 19), (B) intravitreal injection of 1.25 mg of bevacizumab at baseline and 6 weeks (n = 22), (C) intravitreal injection of 2.5 mg of bevacizumab at baseline and 6 weeks (n = 24), (D) intravitreal injection of 1.25 mg of bevacizumab at baseline and sham injection at 6 weeks (n = 22), or (E) intravitreal injection of 1.25 mg of bevacizumab at baseline and 6 weeks with photocoagulation at 3 weeks (n = 22). MAIN OUTCOME MEASURES: Central subfield thickness (CST) on optical coherence tomography and best-corrected visual acuity (VA) were measured at baseline and after 3, 6, 9, 12, 18, and 24 weeks. RESULTS: At baseline, median CST was 411 mum and median Snellen VA equivalent was 20/50. Compared with group A, groups B and C had a greater reduction in CST at 3 weeks and about 1 line better median VA over 12 weeks. There were no meaningful differences between groups B and C in CST reduction or VA improvement. A CST reduction > 11% (reliability limit) was present at 3 weeks in 36 of 84 (43%) bevacizumab-treated eyes and 5 of 18 (28%) eyes treated with laser alone, and at 6 weeks in 31 of 84 (37%) and 9 of 18 (50%) eyes, respectively. Combining focal photocoagulation with bevacizumab resulted in no apparent short-term benefit or adverse outcomes. Endophthalmitis developed in 1 eye. The following events occurred during the first 24 weeks in subjects treated with bevacizumab without attributing cause to the drug: myocardial infarction (n = 2), congestive heart failure (n = 1), elevated blood pressure (n = 3), and worsened renal function (n = 3). CONCLUSION: These results demonstrate that intravitreal bevacizumab can reduce DME in some eyes, but the study was not designed to determine whether treatment is beneficial. A phase III trial would be needed for that purpose.

Verteporfin therapy of subfoveal occult choroidal neovascularization in AMD using delayed light application: one-year results of the VALIO Study.

PURPOSE: To compare photodynamic therapy (PDT) with verteporfin (Visudyne; Novartis Pharma AG, Basel, Switzerland) using either standard or delayed light application. DESIGN: Phase II, multicenter, masked, randomized clinical trial. METHODS: Sixty patients with occult with no classic choroidal neovascularization (CNV) resulting from age-related macular degeneration were assigned randomly (1:1) to verteporfin infusion followed by light application either at 15 minutes (standard light) or 30 minutes (delayed light) after the start of the infusion. The assigned treatment was repeated every three months if fluorescein leakage was detected. RESULTS: At month 12, patients lost a mean of 15.7 letters and 11.4 letters from baseline in the standard and delayed light groups, respectively (P = .38). Twelve (52%) of 23 patients in the standard light group and 11 (42%) of 26 in the delayed light group lost at least 15 letters of visual acuity (P = .57). CONCLUSIONS: There were no statistically significant differences between verteporfin therapy using the delayed light regimen of 30 minutes or the standard light regimen of 15 minutes in eyes with occult with no classic CNV.

Macula Society Collaborative Retrospective Study of Ocriplasmin for Symptomatic Vitreomacular Adhesion.

PURPOSE: To assess anatomic and visual outcomes of ocriplasmin use for symptomatic vitreomacular adhesion (VMA). DESIGN: Retrospective chart review. METHODS: Macula Society members were surveyed online to collect data on ocriplasmin for symptomatic VMA. Clinical and optical coherence tomography data were collected using standardized data entry forms. RESULTS: There were 208 patients (208 eyes) with symptomatic VMA followed at least 3 weeks after receiving ocriplasmin. At baseline, VMA was focal (<1500 µm) in 179 eyes (86%), broad in 9 eyes (4%), and not reported in 20 eyes (10%). A full-thickness macular hole (MH) was present in 75 eyes (36%); size was <400 µm in 62 eyes (82%). Baseline mean visual acuity was approximately 20/63. Of the 204 eyes with ≥12 weeks follow-up, pars plana vitrectomy (PPVx) was performed in 12 (6%) by 4 weeks, 31 (15%) by 12 weeks, and 64 (31%) by the last visit. VMA had resolved by 12 weeks with ocriplasmin alone in 83 of 191 eyes (43%) by week 12 and in 148 of 200 eyes (74%) by the last visit, including eyes undergoing PPVx. Among eyes with a baseline MH, closure was achieved with ocriplasmin alone in 10 of 65 (15%) by 1 week, 26 of 74 (35%) by 4 weeks, and 30 of 75 (40%) at the last visit. Mean change in visual acuity at the last visit compared with baseline was -0.06±0.40 logarithm of the minimum angle of resolution (logMAR) (modest vision improvement) (P = 0.03). At the last visit, visual acuity improved by ≥2 lines in 69 eyes (35%) and by ≥3 lines in 54 eyes (27%). Visual acuity decreased ≥2 lines in 35 eyes (18%) and by 3 lines in 27 eyes (14%) at the final visit. Complications included photopsias (15%), dimness of vision (14%), decreased color vision (10%), MH development (5%), macular retinal pigment epithelium atrophy (2.7%), retinal detachment (1.9%), and retinal tear (1.4%). No endophthalmitis cases were reported. CONCLUSIONS: Physician-reported outcomes on ocriplasmin use confirmed VMA release in 45% and closure of MH in 40% of eyes without PPVx. Visual acuity decreased in approximately 20% of eyes. Adverse events were not infrequent and suggest caution when considering ocriplasmin use.

Implantable miniature telescope for the treatment of visual acuity loss resulting from end-stage age-related macular degeneration: 1-year results.

PURPOSE: To evaluate the safety and efficacy of an implantable visual prosthetic device (IMT; VisionCare Ophthalmic Technologies, Saratoga, CA) in patients with bilateral, end-stage age-related macular degeneration (AMD). DESIGN: Prospective, open-label, multicenter clinical trial with fellow eye controls. PARTICIPANTS: A total of 217 patients (mean age, 76 years) with AMD and moderate to profound bilateral central visual acuity loss (20/80-20/800) resulting from bilateral untreatable geographic atrophy, disciform scars, or both were enrolled. METHODS: A visual prosthetic device (implantable telescope), designed to enlarge retinal images of the central visual field, was implanted monocularly in the capsular bag after lens extraction. Fellow eyes were not implanted to provide peripheral vision and served as controls. Study patients participated in 6 visual rehabilitation visits after surgery. MAIN OUTCOME MEASURES: Best-corrected distance visual acuity (BCDVA) and best-corrected near visual acuity (BCNVA), quality-of-life scores from the National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) and the Activities of Daily Life scale, endothelial cell density (ECD), and incidence of complications and adverse events. RESULTS: At 1 year, 67% of implanted eyes achieved a 3-line or more improvement in BCDVA versus 13% of fellow eye controls (P<0.0001). Fifty-three percent of implanted eyes achieved a 3-line or more improvement in both BCDVA and BCNVA versus 10% of fellow eyes (P<0.0001). Mean BCDVA and BCNVA improved 3.5 lines and 3.2 lines, respectively, in implanted eyes versus 0.8 lines and 1.8 lines, respectively, in fellow eyes (P<0.0001). Change in visual acuity was not related to lesion type. Mean NEI VFQ-25 scores improved by more than 7 points from baseline (P<0.01) on 7 of 8 relevant subscales. Eleven eyes did not receive the device because of an aborted procedure. Endothelial cell density was reduced by 20% at 3 months and 25% at 1 year. The decrease in ECD was correlated with postsurgical edema (P<0.0001), and there was no evidence that endothelial cell loss is accelerated by ongoing endothelial trauma after implantation. CONCLUSIONS: This implantable visual prosthesis can improve visual acuity and quality of life in patients with moderate to profound visual impairment caused by bilateral, end-stage AMD.

Ciliary neurotrophic factor for macular telangiectasia type 2: results from a phase 1 safety trial.

PURPOSE: To evaluate the safety and tolerability of intraocular delivery of ciliary neurotrophic factor (CNTF) using an encapsulated cell implant for the treatment of macular telangiectasia type 2. DESIGN: An open-label safety trial conducted in 2 centers enrolling 7 participants with macular telangiectasia type 2. METHODS: The participant's more severely affected eye (worse baseline visual acuity) received the high-dose implant of CNTF. Patients were followed for a period of 36 months. The primary safety outcome was a change in the parameters of the electroretinogram (ERG). Secondary efficacy outcomes were changes in visual acuity, en face measurements of the optical coherence tomography of the disruption in the ellipsoid zone, and microperimetry when compared with baseline. RESULTS: The ERG findings demonstrated a reduction in the amplitude of the scotopic b-wave in 4 participants 3 months after implantation (month 3). All parameters returned to baseline values by month 12 and remained so at month 36 with no clinical impact on dark adaptation. There was no change in visual acuity compared with baseline. The area of the defect as measured functionally by microperimetry and structurally by the en face OCT imaging of the ellipsoid zone loss appeared unchanged from baseline. CONCLUSIONS: The intraocular delivery of CNTF in the encapsulated cell implant appeared to be safe and well tolerated in eyes with macular telangiectasia type 2. Further evaluation in a randomized controlled clinical trial is warranted to test for efficacy.

Verteporfin therapy for subfoveal choroidal neovascularization in age-related macular degeneration: three-year results of an open-label extension of 2 randomized clinical trials--TAP Report no. 5.

OBJECTIVE: To report vision and safety outcomes from an extension of a 2-year investigation evaluating verteporfin photodynamic therapy in patients with age-related macular degeneration with subfoveal choroidal neovascularization (CNV). DESIGN AND SETTING: Open-label extension of selected patients from 2 multicenter, double-masked, placebo-controlled, randomized clinical trials, the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy (TAP) Investigation, at 22 ophthalmology practices in Europe and North America. PARTICIPANTS: Patients enrolled in the TAP Investigation and followed up for at least 24 months in whom verteporfin therapy to CNV might reduce the risk of further vision loss. METHODS: Before receiving verteporfin therapy in the extension, eligible patients signed a written informed consent form accompanied by an oral consent process approved by local institutional review boards. Methods were similar to those described for 1- and 2-year results, with follow-up examinations beyond 2 years continuing at 3-month intervals with a few exceptions, including that extension patients with fluorescein leakage from CNV were to receive open-label verteporfin therapy irrespective of their original treatment assignment. RESULTS: Of 402 patients in the verteporfin group, 351 (87.3%) completed the month 24 examination; 320 (91.2%) of these enrolled in the extension study. The enrolled participants included 124 (78.0%) of the 159 verteporfin-treated patients with lesions composed of predominantly classic CNV at baseline, of whom 105 (84.7%) completed the month 36 examination. Verteporfin-treated patients with this lesion composition at baseline who participated in the extension study, with or without a month 36 examination, appeared more likely to have a younger age, better level of visual acuity, absence of fluorescein leakage from classic CNV, or no progression of classic CNV beyond the baseline boundaries of the lesion at the month 24 examination compared with those who did not enroll in the extension. For the 105 patients with a predominantly classic baseline lesion composition who completed the month 36 examination, an average of 1.3 treatments were given from the month 24 examination up to, but not including, the month 36 examination. A letter score loss in the study eye of at least 15 from baseline for these patients occurred in 39 (37.5%) at the month 24 examination compared with 44 (41.9%) of these patients at the month 36 examination. Visual acuity changed little from the month 24 examination (mean, -1.9 lines) to the month 36 examination (mean, -2.0 lines) for these eyes. Verteporfin-treated patients had little change in the mean visual acuity lost and few or no additional instances of infusion-related back pain or photosensitivity reactions from month 24 to month 36. Two patients originally assigned to placebo had acute severe vision decrease within 7 days after verteporfin treatment during the extension. One patient originally assigned to verteporfin had acute severe vision decrease after verteporfin treatment of the fellow eye during the extension. CONCLUSIONS: Vision outcomes for verteporfin-treated patients with predominantly classic lesions at baseline remained relatively stable from month 24 to month 36, although only approximately one third of the verteporfin-treated patients originally enrolled with this lesion composition had a month 36 examination. From these results, the TAP Study Group identified no safety concerns to preclude repeating photodynamic therapy with verteporfin. Additional treatment was judged likely to reduce the risk of further vision loss. Caution appears warranted in the absence of comparison with an untreated group during the extension and since not all patients in the TAP Investigation participated in the TAP Extension.