Retinopathy Study Best-corrected Visual Acuity Research Articles

An Evaluation of the Repeatability of Visual Function Following Surgical Repair of Macula-Off Rhegmatogenous Retinal Detachment.

To evaluate the reliability and reproducibility of visual function assessments for patients with macula-off rhegmatogenous retinal detachment (RRD). This prospective study included patients with unilateral macula-off RRD of <10-day duration successfully treated with a single, uncomplicated surgery at least 1 year following repair. Visual function assessments were performed at time of enrollment and 1 month later. Testing included Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), low-contrast visual acuity (VA) 2.5% and 5%, contrast sensitivity assessment with Mars and Gabor patches, reading speed (acuity, speed, and critical print size), color vision testing (protan, deutan, and tritan), and microperimetry. Spectral-domain ocular coherence tomography (SD-OCT) was performed. Paired t-statistics were used to compare values between visits and between the study and fellow eyes. Fourteen patients (9 male, 5 female) with a mean age of 69 years at time of surgery were evaluated. Correlation coefficients across the two visits were highest for ETDRS BCVA (0.97), tritan color vision testing (0.96), and low-contrast VA 5% (0.96), while the average t-statistic was largest for low-luminance deficit (4.2), ETDRS BCVA (4.1), and reading speed critical print size (3.7). ETDRS BCVA did not correlate with SD-OCT findings. ETDRS BCVA can be considered a highly reliable and reproducible outcome measure. LLVA, protan color discrimination, contrast sensitivity, and reading speed may be useful secondary outcome measures. This study provides guidance on the selection of visual function outcome measures for clinical trials of patients with macula-off RRD.

Intravitreal bevacizumab plus propranolol for neovascular age-related macular degeneration (the BEVALOL study): a phase I clinical trial

BackgroundGiven the persistently large public health impact of neovascular age-related macular degeneration (nARMD) despite many years of anti-VEGF therapy as the first-line treatment and the demonstrated ability of b-blockers to reduce neovascularization, a synergistic effect between an anti-VEGF agent and an intravitreal beta-blocker is important to investigate in the quest for therapeutic alternatives that maximize efficacy and/or reduce costs. The main purpose of this study is to investigate the safety of a 0.1 ml intravitreal injection of a combination of bevacizumab (1.25 mg/0.05 ml) and propranolol (50 g/0.05 ml) to treat nARMD.MethodsProspective phase I clinical trial that included patients with nARMD. Comprehensive ophthalmic evaluation was performed at baseline and included Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA), biomicroscopy of the anterior and posterior segments, binocular indirect ophthalmoscopy, color fundus photography, spectral domain optical coherence tomography (OCT), OCT angiography (OCT-A), fluorescein angiography (Spectralis, Heidelberg), and full-field electroretinography (ERG). All eyes were treated with a 0.1 ml intravitreal injection of a combination of bevacizumab (1.25 mg/0.05 ml) and propranolol (50 g/0.05 ml) within 1 week of baseline evaluation. The patients were reexamined at weeks 4, 8 and 12, and clinical evaluation and SD-OCT were performed at all follow-up visits. Additional injections of combination bevacizumab (1.25 mg/0.05 ml) and propranolol (50 g/0.05 ml) were administered at weeks 4 and 8. At the final study evaluation (week 12), color fundus photography, OCT-A, fluorescein angiography, and full-field ERG were repeated.ResultsEleven patients (11 eyes) completed all study visits of the 12 week study. Full field ERG b-waves did not show significant (p < 0.05) changes at week 12 compared to baseline. During the 12 week follow-up period, none of the study eyes developed intraocular inflammation, endophthalmitis or intraocular pressure elevation more than 4 mmHg over baseline. Mean ± SE BCVA (logMAR) was 0.79 ± 0.09 at baseline and was significantly (p < 0.05) improved to 0.61 ± 0.10 at week 4; 0.53 ± 0.10 at week 8; and 0.51 ± 0.09 at week 12. Mean ± SE central subfield thickness (CST) (μm) was 462 ± 45 at baseline and was significantly (p < 0.05) lower at 4, 8 and 12 weeks (385 ± 37; 356 ± 29 and 341 ± 24, respectively).ConclusionsIn this 12 week trial of a combination of intravitreal bevacizumab and propranolol for treatment of nARMD, no adverse events or signals of ocular toxicity were observed. Further studies using this combination therapy are warranted.Trial Registration Project registered in Plataforma Brasil with CAAE number 28108920.0.0000.5440 and approved in ethics committee of Clinics Hospital of Ribeirao Preto Medicine School of São Paulo University—Ribeirão Preto, São Paulo, Brazil (appreciation number 3.999.989 gave the approval).

Two-Year Outcomes After Variable Duration of Drug Cessation in Patients With Maculopathy Associated With Pentosan Polysulfate Use

Prior retrospective studies have provided limited evidence on disease progression following drug cessation in patients with maculopathy associated with pentosan polysulfate (PPS). To evaluate the 2-year evolution of maculopathy associated with PPS use after drug cessation. This cohort study prospectively evaluated the natural history of patients with maculopathy associated with PPS use. Participants seen at the Emory Eye Center were enrolled between December 1, 2018, and December 1, 2019, and data were collected through November 30, 2021. The main outcomes were changes in visual function and structure. Visual function was assessed annually with refraction and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA), mesopic microperimetry, and dark adaptometry. Structural outcomes included presence and extent of complete retinal pigment epithelium and outer retinal atrophy (cRORA), macular central subfield thickness (CST), and subfoveal choroidal thickness (SFCT). Of the 12 participants (23 eyes), 11 (91.7%) were female (1 [8.3%] male), 11 (91.7%) were White (1 [8.3%] Black), and median (IQR) age at enrollment was 58 (47-64) years. Median (IQR) time from PPS discontinuation to initial visit was 0.6 (0.4-1.9) years. Median baseline ETDRS BCVA letter score was 83 (Snellen equivalent, 20/20) (IQR, 80-86.5 [20/25-20/20]), with a median 2-year change of -3 (IQR, -6 to -0.5; P = .08). Four eyes (17.4%) had a letter score decline of 15 or more, all associated with progressive cRORA. Median change in microperimetry average threshold was -3.5 dB (IQR, -4.1 to -2.5 dB; P = .001), and percent reduced threshold was 32.5% (IQR, 20.3%-52.8%; P = .004). Nine eyes (39%) had macular cRORA at baseline, with a median linearized growth rate of 0.23 mm/y (IQR, 0.22-0.25 mm/y). Two eyes (8.7%) without atrophy at baseline developed new-onset cRORA. Median baseline CST was 284 μm (IQR, 253-291 μm), with a median 2-year change of -5 μm (IQR, -13 to 0.5 μm; P = .0497). Median 2-year change in SFCT was 1 μm (IQR, -18 to 16 μm; P = .91). The findings of this cohort study suggest that functional and structural deficits continue to progress in PPS-associated maculopathy even after drug cessation. Additional study is needed to determine whether these findings can be generalized to other patients with PPS-associated maculopathy and whether longer follow-up could determine subsequent disease course.

Two-year results for ranibizumab for radiation retinopathy (RRR): a randomized, prospective trial.

To assess the efficacy of a treat-and-extend strategy with intravitreal ranibizumab for radiation-related macular edema. Forty eyes with radiation-induced macular edema and decreased visual acuity were enrolled in the phase IIb, prospective clinical trial and randomized into 3 cohorts: (A) monthly ranibizumab, (B) monthly ranibizumab with targeted retinal photocoagulation (TRP), or (C) as-needed ranibizumab and TRP. In year 2, all subjects entered a treat-and-extend protocol for ranibizumab. The primary outcome measure was mean change in early treatment diabetic retinopathy study (ETDRS) best-corrected visual acuity (BCVA) from baseline. Through year 1, the mean change in ETDRS BCVA was significantly different between the three cohorts (p < 0.001); cohort A saw the largest gain with + 4.0 letters. Significant anatomic improvements were also seen in all cohorts. Comparatively, through year 2, cohorts A, B, and C had a mean change in ETDRS BCVA of - 1.9, - 3.9, and + 1.3 letters, respectively; additionally, no significant differences were found in absolute ETDRS BCVA across time (ANOVA, p = 0.123). Overall, 90% of eyes maintained VA 20/200 or better and 33.3% of subjects gained at least one line of vision. There were no significant differences in mean central macular thickness for any cohort compared to baseline (p = 0.09). The presence of retinal hemorrhage and intraretinal exudates stayed consistent from year 1 to year 2 for all cohorts. Among eyes with radiation-related macular edema, a treat-and-extend regimen with ranibizumab may not result in as many visual and anatomic improvements as monthly injections. However, treat-and-extend still may prevent serious visual complications compared to historical controls. ClinicalTrials.gov Identifier: NCT02222610.

Visual Function in Pentosan Polysulfate Sodium Maculopathy.

PurposeIndividuals with pentosan polysulfate sodium (PPS) maculopathy commonly report symptoms of prolonged dark adaptation and difficulty reading. We hypothesize that PPS maculopathy causes degradation of visual function not fully captured with visual acuity testing.MethodsSubjects with PPS maculopathy underwent multimodal evaluation of retinal structure and function. Structural changes were graded as moderate or advanced. Patient-reported visual function was assessed with the National Eye Institute Visual Function Questionnaire 39 (NEI-VFQ-39) and Low Luminance Questionnaire (LLQ). Objective functional evaluations included Early Treatment of Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA), Pelli–Robson contrast sensitivity, mesopic microperimetry, and dark adaptometry. Functional testing results were correlated with structural disease category.ResultsThirteen patients (26 eyes), median age 62 years (range, 37–76), completed the study. Median ETDRS letter score was 82 (Snellen equivalent 20/25). Median NEI-VFQ-39 and LLQ composite scores were 65 (range, 33–88) and 41 (range, 20–92), respectively. Median contrast sensitivity was 1.65 (range, 0.15–1.95), and median mesopic microperimetry average thresholds and percent reduced thresholds were 26 decibels (range, 0.4–28.6) and 21.6% (range, 0–100%), respectively. Median rod intercept time was 14.1 minutes (range, 4.4–20.0). Eyes with advanced disease based on retinal structure had significantly worse retinal function for several testing modalities.ConclusionsPPS maculopathy causes considerable visual function degradation that is not fully captured with BCVA testing. There was good correlation between other measures of visual function and disease severity. These findings deepen our concern regarding this patient safety issue.

Individualizing Therapy for Neovascular Age-Related Macular Degeneration with Aflibercept (VITAL): A Two-Year Prospective, Interventional Single-Centre Trial.

AimsTo report the mean change in Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) and reading performance (reading acuity and maximum reading speed (MRS) using the MNREAD test) between baseline and 24 months in treatment-naïve patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept injections.MethodsA prospective, open-label, interventional non-randomised case series with 24 months’ duration. Patients were recruited to the study from medical retina clinics at Moorfields Eye Hospital. Intravitreal injections of 2.0 mg aflibercept in the study eye were administered using a fixed dosing regimen during the first year and a treat-and-extend treatment regimen during the second year of treatment.ResultsFifty patients were enrolled with a mean age (SD) of 78.7 (7.6) years; a mean BCVA of 62.8 ETDRS letters; mean reading acuity of 0.52 logMAR; mean maximum reading speed (MRS) of 141.3 words per minute and a central macular thickness of 322.6 µm at baseline. The mean improvement in BCVA was 6.4 letters for the 44 patients (88%) for whom data was available at 2 years. The mean improvement in reading acuity was 0.13 logMAR with an improvement in MRS of 2.9 words per minute. The mean reduction in CRT from baseline was 104.8 µm.ConclusionsAflibercept treatment of nAMD using fixed dosing in year 1 and treat and extend in year 2 leads to improvements in reading ability, visual acuity and retinal morphology which were maintained to 2 years of treatment.Trial RegistrationClinicalTrials.gov Identifier NCT02441816, the VITAL study.Electronic supplementary materialThe online version of this article (10.1007/s40123-020-00267-5) contains supplementary material, which is available to authorized users.

POSTOPERATIVE MOVEMENT OF THE FOVEA AFTER SUCCESSFUL SURGERY IN PATIENTS WITH IDIOPATHIC EPIRETINAL MEMBRANES.

To evaluate the change in the fovea's postoperative location after successful pars plana vitrectomy with combined epiretinal and internal limiting membrane peeling in patients with idiopathic epiretinal membranes (iERMs). In this prospective study 32 eyes of 32 patients with iERMs were followed from baseline before until 3 months after surgery. Study measures included 4-m Early Treatment Diabetic Retinopathy Study best-corrected visual acuity, enhanced-depth imaging-optical coherence tomography, and intraoperative fundus photographs. Foveal movement was assessed by measuring the change in the papillofoveal distance (∆PFD). Mean ∆PFD in the study eye was -124 µm (±138) and -272 µm (±213) one day and 3 months after surgery, respectively. Mean ∆PFD after 3 months was greater in the study than in the fellow eye (P < 0.001). ∆PFD at Month 3 did not correlate with the internal limiting membrane area peeled (P = 0.78). Foveal movement starts immediately after surgery and causes a statistically significant reduction in PFD after uneventful macular pucker surgery. ∆PFD correlates statistically significantly with baseline best-corrected visual acuity and baseline central retinal thickness. The internal limiting membrane peeling size had no significant effect on the amount of postoperative foveal dislocation.

CONBERCEPT IN PATIENTS WITH TREATMENT-NAIVE NEOVASCULAR AGE-RELATED MACULAR DEGENERATION IN REAL-LIFE SETTING IN CHINA

In this study, we aimed to evaluate the efficacy and safety of intravitreal conbercept in patients with treatment-naive neovascular age-related macular degeneration in real-life setting. Three consecutive intravitreal injections of conbercept following a pro re nata protocol. The main outcomes were the changes of Early Treatment Diabetic Retinopathy Study best-corrected visual acuity and central retinal thickness between the baseline and the 12th month. Mean best-corrected visual acuity was improved from 39.39 ± 24.91 letters at the baseline to 44.26 ± 22.89 letters at the final follow-up (P < 0.001). At the 12th month, the proportion of optimal response was 43.48% compared with 36.96% of poor response and 19.56% of nonresponse. A mean central retinal thickness of 480.94 ± 178.47 μm at the baseline was significantly reduced to 366.33 ± 173.52 μm at the 12th month. Patients received a median of 5.32 intravitreal injections. At the 12th month, the mean change in best-corrected visual acuity of eyes with intraretinal cystoid fluid from the baseline was markedly lower than that of eyes without intraretinal cystoid fluid. No adverse events were attributed to conbercept. With 12-month follow-up, conbercept was proved to be an effective and safety treatment for patients with treatment-naive neovascular age-related macular degeneration in real-life setting.

Rehabilitation with biofeedback training in age-related macular degeneration for improving distance vision

Biofeedback training (BT) is a modern method for enhancing the use of preferred retinal loci (PRL) retraining for new retinal loci (TRL), hence improving far and near vision. This article attempts to clarify the optimal methodology for BT and the types of patients who can benefit most from BT. This is a retrospective review of cases who received BT with the macular integrity assessment (MAIA) microperimetre. Outcome measures selected for analysis were visual acuity, PRL location, fixation stability, fixation pattern orientation, reading acuity, critical print size, and reading speed. Out of 30 cases who received BT, only those with age-related macular degeneration and visual acuity of logMAR 0.8 (20/126) or poorer showed a visual acuity gain (statistically significant of 12 letters) after BT. Those with other diagnoses and those with residual Early Treatment Diabetic Retinopathy Study best-corrected visual acuity of logMAR of 0.7 (20/100) or better showed only positive trends for visual acuity and a negative trend for fixation stability. All subjects showed a shift in PRL location toward the superior quadrant of the retina (p < 0.02) in those who received BT. BT seems to offer patients a unique and efficient modality to improve distance vision outside of using optical devices.

Targeted Retinal Photocoagulation for Diabetic Macular Edema with Peripheral Retinal Nonperfusion: Three-Year Randomized DAVE Trial

To evaluate the effect of targeted retinal photocoagulation (TRP) on visual and anatomic outcomes and treatment burden in eyes with diabetic macular edema (DME). Phase I/II prospective, randomized, controlled clinical trial. Forty eyes of 29 patients with center-involved macular edema secondary to diabetes mellitus. Eyes with center-involved DME and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) between 20/32 and 20/320 (Snellen equivalent) were randomized 1:1 to monotherapy with 0.3 mg ranibizumab (Lucentis, Genentech, South San Francisco, CA) or combination therapy with 0.3 mg ranibizumab and TRP guided by widefield fluorescein angiography. All eyes received 4 monthly ranibizumab injections followed by monthly examinations and pro re nata (PRN) re-treatment through 36 months. Targeted retinal photocoagulation was administered outside the macula to areas of retinal capillary nonperfusion plus a 1-disc area margin in the combination therapy arm at week 1, with re-treatment at months 6, 18, and 25, if indicated. Mean change in ETDRS BCVA from baseline and number of intravitreal injections administered. At baseline, mean age was 55 years, mean BCVA was 20/63 (Snellen equivalent), and mean central retinal subfield thickness (CRT) was 530 μm. Thirty-four eyes (85%) completed month 36, at which point mean BCVA improved 13.9 and 8.2 letters (P= 0.20) and mean CRT improved 302 and 152 μm (P= 0.03) in the monotherapy and combination therapy arms, respectively. The mean number of injections administered through month 36 was 24.4 (range, 10-34) and 27.1 (range, 12-36), with 73% (362/496) and 80% (433/538) of PRN injections administered (P= 0.004) in the monotherapy and combination therapy arms, respectively. Goldmann visual field isopter III-4e area decreased by 2% and 18% in the monotherapy and combination therapy arms, respectively (P= 0.30). In this 3-year randomized trial of 40 eyes with DME, there was no evidence that combination therapy with ranibizumab and TRP improved visual outcomes or reduced treatment burden compared with ranibizumab alone.

Simple Single-Pass Technique for Ultrathin Descemet Stripping Automated Endothelial Keratoplasty: A Pilot Study.

To assess intraoperative and postoperative graft thickness (GT) after donor deturgescence for ultrathin Descemet stripping automated endothelial keratoplasty and to evaluate visual outcomes, endothelial cell density, and patient satisfaction at 1 year. Prospective interventional case series of patients with Fuchs endothelial dystrophy, Fuchs endothelial dystrophy and cataract, and pseudophakic bullous keratopathy (n = 12 grafts). The donor cornea was allowed to thin out by simple evaporation on an artificial anterior chamber, to the required precut thickness, before a single microkeratome pass. GT after microkeratome cut, at 1 week, 1, 3, 6, and 12, months was measured. Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity, Pelli-Robson contrast sensitivity, endothelial cell density, and score on the visual function questionnaire (VFQ-25) were assessed. Mean intraoperative postmicrokeratome cut GT was 78.9 ± 33.3 μm. Mean GT at 1 week, 1, 3, 6, and 12 months was 70.7, 70.9, 62.8, 66.5, and 58.9 μm, respectively. Mean initial donor corneal thickness was 647 ± 67 μm, and mean precut thickness was 526 ± 4.5 μm (mean thinning time: 17 min). Best-corrected visual acuity at 1 week, 1, 3, 6, and 12 months was 68.8, 76.9, 76.3, 76.9, and 78.6 letters with 9-letter gain at 12 months (P = 0.02). Mean endothelial cell loss at 3, 6, and 12 months was 36.8% ± 6.75%, 37.2% ± 8%, and 37.9% ± 9.75% loss, respectively. At 1 year, 83.3% of patients achieved ≥20/40 (6/12) and 66.7% of patients achieved ≥20/32 (6/9.5). VFQ-25 testing showed an improvement in the visual function. This pilot study demonstrates a simple graft deturgescence technique that reproducibly creates ultrathin grafts without donor wastage.

Photodynamic therapy in chronic central serous chorioretinopathy with subretinal fluid outside the fovea

PurposeTo assess the efficacy of photodynamic therapy (PDT) in patients with chronic central serous chorioretinopathy (cCSC), in whom subretinal fluid (SRF) was solely present outside the foveal area.MethodsIn this retrospective study, 16 eyes of 15 cCSC patients who received half-dose PDT because of notable subjective visual complaints due to the presence of extrafoveal SRF, were included. An ophthalmic examination was performed before treatment, including Early Treatment Diabetic Retinopathy Study best-corrected visual acuity measurement, applanation tonometry, slit-lamp examination, and indirect ophthalmoscopy, followed by multimodal imaging, including fundus photography, fundus autofluorescence, spectral-domain optical coherence tomography (OCT), enhanced-depth imaging OCT of the choroid, fluorescein angiography, and indocyanine green angiography.ResultsIn 7 treated patients (47%), PDT led to a decrease in visual complaints at the first evaluation visit. At this visit, extrafoveal SRF on OCT had resolved in 14 eyes (88%), whereas a complete resolution of extrafoveal SRF had occurred in all eyes at final follow-up visit. At baseline, posterior cystoid retinal degeneration was also present in 5 eyes (31%) and this remained present at all evaluation visits in these patients. Choroidal thickness decreased statistically significantly in the treated eyes, both foveally and at the location of the maximum height of extrafoveal SRF. No complications of PDT were observed.ConclusionsHalf-dose PDT treatment of cCSC patients with visual complaints due to extrafoveal SRF accumulation is a safe procedure leading to complete SRF resolution, a decrease in choroidal thickness, and a reduction in visual symptoms.

Randomized Trial of Treat-and-Extend versus Monthly Dosing for Neovascular Age-Related Macular Degeneration: 2-Year Results of the TREX-AMD Study

To evaluate a prospective treat-and-extend (TREX) management strategy compared with monthly dosing with intravitreal ranibizumab (Lucentis) in neovascular age-related macular degeneration (AMD). Prospective, randomized, multicenter clinical trial. Sixty patients with treatment-naïve neovascular AMD randomized 1:2 to monthly or TREX cohorts. Patients with Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) of 20/32 to 20/500 (Snellen equivalent) were randomized to receive intravitreal 0.5 mg ranibizumab monthly or, according to a TREX protocol, no less frequently than every 12 weeks. After interval extension, if recurrent exudative disease was identified, this maximum interval between treatments was rechallenged according to a strict prospective protocol. Change in ETDRS BCVA from baseline. Sixty patients were enrolled and 50 completed month 24, at which point mean ETDRS BCVA letter gains were similar: 10.5 and 8.7 for the monthly and TREX cohorts, respectively (P= 0.64). At month 24, 4 patients (20%) and 12 patients (30%) in the monthly and TREX cohorts, respectively, gained at least 15 letters (P= 0.41). No monthly cohort patient lost more than 2 letters, whereas 5 TREX cohort patients (13%) lost at least 15 letters. Anatomic improvements were similar between the cohorts. Through month 24, the mean number of injections administered was 25.5 (range, 22-27) and 18.6 (range, 10-25) for the monthly and TREX cohorts, respectively (P< 0.001). Among TREX patients completing month 24, 14 (47%) were at an extension interval of 8 weeks or more, and the mean maximum tolerated extension was 8.5 weeks over the course of 2 years. Of the 26 TREX patients (65%) who demonstrated recurrent exudation upon interval extension, the first maximum extension interval was consistent in most eyes (n= 19 [73%]). The TREX neovascular AMD management protocol used with ranibizumab in the Treat-and-Extend Protocol in Patients with Wet Age-Related Macular Degeneration (TREX-AMD) study resulted in visual and anatomic gains comparable with those obtained with monthly dosing, and most patients randomized to TREX therapy demonstrated a relatively consistent maximum extension interval.

Neovascular age-related macular degeneration without drusen in the fellow eye: clinical spectrum and therapeutic outcome.

PurposeTo investigate the clinical characteristics and therapeutic outcome of patients with neovascular age-related macular degeneration (nAMD) in 1 eye, without drusen in the fellow eye.Patients and methodsMedical records of 381 patients were analyzed to identify the cases. The main outcomes included Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) and change in central retinal thickness (CRT). These parameters were reviewed at baseline, first follow-up visit, and after 6, 12, and 24 months.ResultsOut of 381 patients, 29 cases (8%) were included (of whom 3 had polypoidal choroidal vasculopathy [PCV]) who were treated with anti-vascular endothelial growth factor (anti-VEGF) therapy which was supplemented by photodynamic therapy (PDT) in the PCV patients. Overall, no statistically significant change in mean BCVA was observed during follow-up. BCVA improved or remained stable (defined as a gain in BCVA, a stable BCVA, or a loss of <5 ETDRS letters) in 22 patients (76%), and 7 patients (23%) had lost ≥5 ETDRS letters at final follow-up. A gain of ≥15 ETDRS letters at final follow-up was seen in 5 patients (17%). Mean CRT had decreased significantly with 99 µm (P<0.001) at 24 months after the initial visit.ConclusionThere is a clinical spectrum of nAMD that is not associated with drusen in the fellow eye. Patients with nAMD without drusen in the fellow eye respond to anti-VEGF treatment and, in cases of PCV, to supplemental PDT. The pathophysiology of this spectrum of nAMD may be different from drusen-associated age-related macular degeneration.

Epimacular Brachytherapy for Previously Treated Neovascular Age-Related Macular Degeneration (MERLOT): A Phase 3 Randomized Controlled Trial

To assess the safety and efficacy of epimacular brachytherapy (EMB) for patients with chronic, active, neovascular age-related macular degeneration (AMD). Phase 3 randomized controlled trial. Patients (n= 363) with neovascular AMD already receiving intravitreal ranibizumab injections. Either pars plana vitrectomy with 24-gray EMB and ongoing pro re nata (PRN) ranibizumab (n=224) or ongoing PRN ranibizumab monotherapy (n= 119). The coprimary outcomes, at 12 months, were the number of PRN ranibizumab injections and Early Treatment of Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (VA). Secondary outcomes included the proportion of participants losing fewer than 15 ETDRS letters, angiographic total lesion size, choroidal neovascularization (CNV) size, and optical coherence tomography (OCT) foveal thickness. A predefined subgroup analysis tested the influence of baseline ocular characteristics on the response to EMB. The mean number of PRN ranibizumab injections was 4.8 in the EMB arm and 4.1 in the ranibizumab monotherapy arm (P= 0.068). The mean VA change was-4.8 letters in the EMB arm and-0.9 letters in the ranibizumab arm (95% confidence interval of difference between groups,-6.6 to-1.8 letters). The proportion of participants losing fewer than 15 letters was 84% in the EMB arm and 92% in the ranibizumab arm (P= 0.007). In the EMB arm, the mean total lesion size increased by 1.2 mm(2) versus 0.4 mm(2) in the ranibizumab arm (P= 0.27). The CNV size decreased by 0.5 mm(2) in the EMB arm and by 1.3 mm(2) in the ranibizumab arm (P= 0.27). The OCT foveal thickness decreased by 1.0 μm in the EMB arm and by 15.7 μm in the ranibizumab arm (P= 0.43). Most subgroups favored ranibizumab monotherapy, some significantly so. One participant showed retinal vascular abnormality attributed to radiation, but otherwise safety was acceptable. These results do not support the use of EMB for chronic, active, neovascular AMD. Safety isacceptable out to 12 months, but radiation retinopathy can occur later, so further follow-up is planned.

Prospective Trial of Treat-and-Extend versus Monthly Dosing for Neovascular Age-Related Macular Degeneration: TREX-AMD 1-Year Results

To assess prospectively a treat-and-extend (TREX) management strategy compared with monthly dosing of intravitreal ranibizumab in treatment-naïve neovascular age-related macular degeneration (AMD) patients. Phase IIIb, multicenter, randomized, controlled clinical trial. Sixty patients with treatment-naïve neovascular AMD randomized 1:2 to monthly or TREX management. Patients with Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) from 20/32 to 20/500 (Snellen equivalent) were randomized to receive intravitreal 0.5 mg ranibizumab monthly or according to a TREX protocol. The TREX patients were treated monthly for at least 3 doses, until resolution of clinical and spectral-domain optical coherence tomography evidence of exudative disease activity; the interval between visits then was individualized according to a strict prospective protocol. Mean ETDRS BCVA change from baseline. At baseline, mean age was 77 years (range, 59-96 years), mean BCVA was 20/60 (Snellen equivalent), and mean central retinal thickness (CRT) was 511 μm. Fifty-seven eyes (95%) completed month 12, at which point mean BCVA improved by 9.2 and 10.5 letters in the monthly and TREX cohorts, respectively (P = 0.60). The mean number of injections administered through month 12 was 13.0 and 10.1 (range, 7-13) in the monthly and TREX cohorts, respectively (P < 0.0001). Among TREX patients, 7 (18%) were maximally extended, 4 (10%) demonstrated fluid at every visit, and at month 12, 18 (45%) had achieved an extension interval of 8 weeks or more; the mean maximum extension interval between injections after the first 3 monthly doses was 8.4 weeks (range, 4-12 weeks). Most TREX patients who demonstrated recurrent exudative disease activity (17/24 [71%]) were unable to extend beyond their initial maximum extension interval. The TREX neovascular AMD management strategy used in this prospective, randomized, controlled trial resulted in visual and anatomic gains comparable with those obtained with monthly dosing.

Results of intravitreal dexamethasone implant 0.7 mg (Ozurdex®) in non-infectious posterior uveitis.

To evaluate the safety and efficacy of dexamethasone implant in patients with non-infectious posterior uveitis with cystoid macular edema (CME). Retrospective analysis of patients reports with CME secondary to non-infectious uveitis treated with dexamethasone implant. Data included type of posterior uveitis, any systemic immunosuppressive therapy, Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA), central macular thickness (CMT) on optical coherence tomography (OCT) and signs of intraocular inflammation at baseline and then at 2wk postoperatively and monthly thereafter. Follow-up is up to 10mo. Any per-operative and post-operative complications were recorded. Six eyes of 4 patients with CME due to non-infectious posterior uveitis treated with dexamethasone implant. Diagnosis included idiopathic panuveitis, birdshot chorioretinopathy and idiopathic intermediate uveitis. At baseline mean ETDRS BCVA was 63 letters and mean CMT 556 µm at 2wk postoperatively mean ETDRS BCVA improved to 70 letters and mean CMT decreased to 329 µm. All eyes showed clinical evidence of decreased inflammation. The duration of effect of the implant was 5 to 6mo and retreatment was required in 2 eyes. Two patients required antiglaucoma therapy for increased intraocular pressures. In patients with non-infectious posterior uveitis dexamethasone implant can be a short-term effective treatment option for controlling intraocular inflammation.

Therapeutic benefit of melatonin in refractory central serous chorioretinopathy.

To evaluate the efficacy and safety of melatonin for the treatment of chronic central serous chorioretinopathy (CSCR). Prospective comparative case series. A total of 13 patients with chronic CSCR were treated for 1 month: 8 patients were treated orally with 3 mg melatonin t.i.d., and 5 with placebo. All patients had 20/40 or worse Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) in the affected eye or presented an incapacitating scotoma. Most of the patients had previous failed treatments for their condition. Observational procedures included ETDRS BCVA, and complete ophthalmic examination. Optical coherence tomography (OCT) was performed at day 1 and week 4. Fluorescein angiography was performed at baseline only for diagnostic purposes. Data were subjected to two-sample t-test statistical analysis. P-values of <0.05 were considered statistically significant. At 1-month follow-up, BCVA significantly improved in 87.5% of patients treated with melatonin (7 of 8 patients, P<0.05). All patients showed a mean significant reduction (P<0.01) of central macular thickness (CMT) when compared with the baseline, with 3 patients (37.5%) exhibiting complete resolution of subretinal fluid at 1-month follow-up. No significant side effects were observed. No changes in BCVA or CMT were noted in the control group. These results suggest that melatonin is safe, well tolerated, and effective in the treatment of chronic CSCR, as it significantly improved BCVA and CMT in patients with this pathology. Further evaluations with longer follow-up and a larger patient population are desirable.

Serous Retinopathy Associated with Mitogen-Activated Protein Kinase Kinase Inhibition (Binimetinib) for Metastatic Cutaneous and Uveal Melanoma

To analyze the clinical characteristics of a serous retinopathy associated with mitogen-activated protein kinase kinase (MEK) inhibition with binimetinib treatment for metastatic cutaneous melanoma (CM) and uveal melanoma (UM), and to determine possible pathogenetic mechanisms that may lead to this retinopathy. Prospective observational, cohort-based, cross-sectional study. Thirty CM patients and 5 UM patients treated with the MEK inhibitor binimetinib (CM) or a combination of binimetinib and the protein kinase C inhibitor sotrastaurin (UM). Extensive ophthalmic examination was performed, including Early Treatment of Diabetic Retinopathy Study best-corrected visual acuity, applanation tonometry, slit-lamp examination, indirect ophthalmoscopy, digital color fundus photography, and optical coherence tomography (OCT). In selected cases, additional examinations were performed, including visual field testing and electro-oculography (EOG). Blood samples were obtained from 3 CM patients and 3 UM patients to analyze the presence of autoantibodies against retinal and retinal pigment epithelium (RPE) proteins. Visual symptoms, visual acuity, fundus appearance, characteristics on OCT, fundus autofluorescence (FAF), and EOG. Six CM patients (20%) and 2 UM patients (40%) reported visual symptoms during the study. The median time to the onset of symptoms, which were all mild and transient, was 3.5 days (range, <1 hour to 3 weeks). On OCT, subretinal fluid (SRF) was detected in 77% of CM patients and 60% of UM patients. In the 26 patients with SRF, the fovea was affected in 85%. After the start of the medication, an EOG was performed in 19 eyes of 11 patients; 16 of these eyes (84%) developed SRF on OCT. Fifteen of these eyes (94%) showed an abnormal Arden ratio (<1.65). A broad pattern of anti-retinal antibodies was found in 3 CM patients and 2 UM patients tested, whereas anti-RPE antibodies were detected in all 6 tested patients. A time-dependent and reversible serous retinopathy can develop both in patients with metastatic CM and UM treated with binimetinib. A minority of patients develop visual symptoms, which are generally mild and transient. A cause of binimetinib-associated serous retinopathy may be toxicity of medication, but autoantibodies also may be involved.

Nondamaging photothermal therapy for the retina: initial clinical experience with chronic central serous retinopathy.

To assess safety and clinical efficacy of the nondamaging photothermal therapy for the macula for the treatment of chronic central serous retinopathy. Sixteen eyes of 16 patients with persistent central serous retinopathy (>4 months of duration) were treated with the PASCAL Streamline) at 577-nm wavelength, using 200-μm retinal spot sizes. Using Endpoint Management Software, the laser power was first titrated for a barely visible burn with 15-ms pulses, which was defined as 100% pulse energy. Treatment was then applied over the area of serous retinal detachment and adjacent nonthickened retina, using 30% pulse energy with the spot spacing of 0.25 beam diameter. Changes in subretinal fluid, Early Treatment Diabetic Retinopathy Study best-corrected visual acuity, and central macular thickness were measured over 6 months of follow-up. Pretreatment and posttreatment fluorescein angiography and fundus autofluorescence were also assessed. On average, 532 spots have been applied per treatment. No visible laser marks could be detected by clinical observation, optical coherence tomography, fundus autofluorescence, or fluorescein angiography. On average, 12 Early Treatment Diabetic Retinopathy Study letters gain was achieved at 2 months and was sustained by 6 months (P < 0.001). Central macular thickness decreased from 350 μm to 282 μm (P = 0.004). Subretinal fluid completely resolved in 37% of the patients after first treatment, whereas 44% of the patients required retreatment after 3 months because of recurrent fluid or incomplete resolution. The remaining 19% of the patients received a second retreatment. By 6 months, in 75% of the patients, the subretinal fluid was completely resolved, whereas in 25%, there was some minimal fluid left. Photothermal therapy using 577-nm PASCAL laser with Endpoint Management graphic user interface was safe, and it improved visual acuity and resolution of subretinal fluid in chronic central serous retinopathy. Lack of tissue damage allows periodic retreatment without cumulative scaring, characteristic to conventional photocoagulation. This technique should be tested in the treatment of other macular disorders and may offer an alternative to conventional laser coagulation of the macula and to anti-vascular endothelial growth factor pharmacological treatments of macular diseases.