ETDRS Best-corrected Visual Acuity Research Articles

Phase I Study of Intravitreal Injection of Autologous CD34+ Stem Cells from Bone Marrow in Eyes with Vision Loss from Retinitis Pigmentosa

PurposeTo evaluate the feasibility and safety of intravitreal injection of autologous CD34+ stem cells from bone marrow (BMSCs) in eyes with vision loss from retinitis pigmentosa (RP). DesignPhase I prospective open-labeled single center study. ParticipantsSeven eyes (7 patients) with RP with best corrected visual acuity (BCVA) of 20/100 to 20/400 or visual field constriction to within 10 degrees. MethodsA comprehensive exam with ETDRS BCVA, macular optical coherence tomography, perimetry, fluorescein angiography was performed at baseline, 1 to 3 months, and 6 months after study treatment. Bone marrow aspiration, isolation of CD34+ BMSCs under Good Manufacturing Practice (GMP) conditions, and intravitreal cell injection were performed on the same day. The CD34+ cells were isolated from bone marrow using a Ficoll gradient and the Miltenyi CliniMACs system. Isolated CD34+ cells were released for clinical use if viability, sterility and purity met the release criteria accepted by the Food and Drug Administration for this clinical study. Main Outcome MeasuresNumber of CD34+ cells isolated for injection and adverse events associated with study treatment during follow-up. Secondary outcome measures are changes in BCVA and perimetry. ResultsAll isolated CD34+ cells passed the release criteria. A mean of 3.26 + 0.66 million viable CD34+ cells (range 1.6 to 7.05 million) were injected intravitreally per eye. No adverse event was noted during the study follow-up except for one participant who was noted with transient cells in the anterior chamber with mild elevation in intraocular pressure at 18 hours after study injection which normalized by 24 hours. BCVA remained within 2 lines of baseline or improved in all participants at 6 months follow-up. Perimetry was stable or improved in all eyes during study follow-up except one eye with transient improvement at 1 month and worsening of both eyes at 6 months. ConclusionIntravitreal injection of autologous CD34+ BMSCs is feasible and appears to be well tolerated in eyes with vision loss from RP. A larger randomized prospective study would be needed to evaluate further the safety and potential efficacy of this cell therapy for vision loss associated with RP.

Magnitude of Visual Acuity Change with ETDRS versus Snellen Testing in Clinical Trials: Implications for Clinic-Based Outcomes

To compare visual acuity (VA) changes using standardized ETDRS best-corrected visual acuity (BCVA) and nonstandardized Snellen VA among subjects enrolled in clinical trials. Retrospective study. Patients enrolled in prospective clinical trials at 3 urban retina practices. Best available Snellen VA at the clinic visit before study entry and after exit were compared with the ETDRS BCVA at trial entry and exit. The correlation and discrepancies between Snellen VA and ETDRS methods as well as the VA changes from trial entry to exit were evaluated. The discrepancy between VA change from trial entry to exit using Snellen VA versus ETDRS BCVA methods. A total of 273 eyes were included. The mean (standard deviation [SD]) Snellen VA was 58.1 (20) ETDRS-equivalent letters (Snellen 20/69) at the clinic visit before trial entry and 61.6 (21) ETDRS-equivalent letters (Snellen 20/59) at the visit after trial exit. The mean (SD) ETDRS BCVA was 65.5 (16) letters (Snellen 20/49) at trial entry and 70.5 (17) letters (Snellen 20/39) at trial exit. The mean VA change from trial entry to exit was not significantly different for ETDRS (5 letters of vision gain) compared with Snellen (3.6 letters of vision gain) methods (P= 0.061). Eyes with baseline Snellen VA 20/50 or worse gained significantly more letters using Snellen (9.3±22.3 letters) compared with ETDRS (5.2 ± 18.7 letters; P= 0.012). Among eyes with baseline Snellen VA of > 20/50, VA gain was significantly greater with the ETDRS method (4.9 ± 12.3 letters) compared with Snellen (-1.5 ± 12.3 letters; P < 0.001). The mean VA change from clinical trial entry to exit was similar between the ETDRS and Snellen methods. However, among patients with worse baseline Snellen vision, the magnitude of VA change was greater with Snellen compared with ETDRS, whereas among those with better baseline vision, this magnitude was greater with the ETDRS method. Understanding the proportion of the study population with varying VA levels may have implications for interpreting VA outcomes from retrospective clinic-based studies compared with those reported in clinical trials. Proprietary or commercial disclosure may be found after the references.

Maximal Extension Interval and Visual Outcomes in a Treat-and-Extend Protocol: A Post Hoc Analysis of the CANTREAT Randomized Trial

Introduction: The Canadian Treat-and-Extend Analysis Trial with Ranibizumab (CANTREAT) was a 2-year, multicentred, randomized clinical trial to evaluate treat-and-extend (T&E) relative to monthly administration of ranibizumab in neovascular age-related macular degeneration (nAMD). This post hoc analysis of the CANTREAT trial explores the relationship between the maximal extension interval tolerated by patients receiving T&E ranibizumab and visual acuity outcomes. Methods: Treatment-naïve patients with nAMD were randomized to receive either a once-monthly dosing or T&E regimen of ranibizumab across 27 treatment centres in Canada and were followed for 24 months. For this post hoc analysis, patients in the T&E cohort were subdivided into the following groups based on maximum extension interval: 4 weeks, 6 weeks, 8 weeks, 10 weeks, and 12 weeks. The primary outcome was the change in ETDRS best-corrected visual acuity (BCVA) from baseline to month 24 while secondary outcomes included change in central retinal thickness (CRT). All results were reported using descriptive statistics. Results: A total of 285 participants undergoing T&E were enrolled in this post hoc analysis. At month 24, the change in BCVA from baseline was +8.5 ± 9.3, +7.7 ± 13.8, +4.4 ± 9.6, +4.4 ± 18.5, and +7.8 ± 14.8 letters in the 4-, 6-, 8-, 10-, and 12-week cohorts, respectively. The change in CRT at month 24 was −79.2 ± 95.0, −143.9 ± 128.9, −97.7 ± 101.1, −120.9 ± 105.3, and −133.2 ± 108.8 μm in the 4-, 6-, 8-, 10-, and 12-week cohorts, respectively. Conclusion: The capacity to extend does not necessarily associate with improved visual acuity outcomes, with the poorest change in BCVA seen in those extended 8–10 weeks. The highest change in BCVA and lowest decrease in CRT was in the group maximally extended for 4 weeks. There was a correlation between change in BCVA and change in CRT for other extension groups. Future studies should establish the predictive factors for successful extension in patients undergoing T&E in nAMD.

A Randomized Controlled Trial of OPT-302, a VEGF-C/D Inhibitor for Neovascular Age-Related Macular Degeneration

Neovascular (wet) age-related macular degeneration (nAMD) is driven by VEGFs A, C, and D, which promote angiogenesis and vascular permeability. Intravitreal injections of anti-VEGF-A drugs are the standard of care, but these do not inhibit VEGF-C and D, which may explain why many patients fail to respond fully. This trial aimed to test the safety and efficacy of OPT-302, a biologic inhibitor of VEGF-C and D, in combination with the anti-VEGF-A inhibitor ranibizumab. Dose-ranging, phase 2b, randomized, double-masked, sham-controlled trial. Participants with treatment-naive nAMD were enrolled from 109 sites across Europe, Israel, and the United States. Participants were randomized to 6, 4-weekly, intravitreal injections of 0.5 mg OPT-302, 2.0 mg OPT-302, or sham, plus intravitreal 0.5 mg ranibizumab. The primary outcome was mean change in ETDRS best-corrected visual acuity (BCVA) at 24 weeks. Secondary outcomes (comparing baseline with week 24) were the proportion of participants gaining or losing ≥ 15 ETDRS BCVA letters; area under the ETDRS BCVA over time curve; change in spectral-domain OCT (SD-OCT) central subfield thickness; and change in intraretinal fluid and subretinal fluid on SD-OCT. Of 366 participants recruited from December 1, 2017, to November 30, 2018, 122, 123, and 121 were randomized to 0.5 mg OPT-302, 2.0 mg OPT-302, and sham, respectively. Mean (± standard deviation) visual acuity gain in the 2.0 mg OPT-302 group was significantly superior to sham (+14.2 ± 11.61 vs.+10.8 ± 11.52 letters; P= 0.01). The 0.5 mg OPT-302 group was not significantly different than the sham group (+9.44 ± 11.32 letters; P= 0.83). Compared with sham, the secondary BCVA outcomes favored the 2.0 mg OPT-302 group, with structural outcomes favoring both OPT-302 dosage groups. Adverse events (AEs) were similar across groups, with 16 (13.3%), 7 (5.6%), and 10 (8.3%) participants in the lower-dose, higher-dose, and sham groups, respectively, developing at least 1 serious AE. Two unrelated deaths both occurred in the sham arm. Significantly superior vision gain was observed with OPT-302 2.0 mg combination therapy, versus standard of care, with favorable safety (ClinicalTrials.gov identifier: NCT03345082). Proprietary or commercial disclosure may be found after the references.

The Optical Coherence Tomography and Microperimetry Biomarker Evaluation in Patients with Geographic Atrophy (OMEGA) Study: Design and Baseline Characteristics – OMEGA Report 1

Introduction: The aim of this study was to describe the design and the participants’ baseline characteristics of a prospective natural history study of geographic atrophy (GA) secondary to age-related macular degeneration. Methods: The optical coherence tomography (OCT) and microperimetry biomarker evaluation in patients with GA (OMEGA) study was conducted at a tertiary referral center (ClinicalTrials.gov identifier: NCT05963646). Participants were followed for 12 months during 4 visits (baseline and follow-up exams at weeks 12, 24, and 48) with best-corrected Early Treatment of Diabetic Retinopathy Study visual acuity, low-luminance visual acuity (LLVA), and quick contrast sensitivity function testing. Further, participants underwent spectral-domain OCT, OCT angiography, fundus autofluorescence imaging, and mesopic microperimetry testing. Results: Thirty participants (median [IQR] age of 79 [77, 84] years) and 37 study eyes were included with a (median [IQR]) GA area of 1.40 mm2 (0.49, 5.24) at baseline. Out of 37 study eyes, six developed macular neovascularizations (16%). The study-eye best-corrected visual acuity was (median [IQR]) 0.18 logarithm of the minimum angle of resolution (logMAR) (0.06, 0.26), LLVA 0.66 logMAR (0.36, 0.88), and the microperimetry mean sensitivity 18.4 dB (9.21, 20.9). The highest correlation between square root GA area and a visual function test was evident for LLVA (R2 of 0.578), followed by area under the log contrast sensitivity function curve (0.519) and microperimetral retinal sensitivity (0.487). Conclusion: This report lays out the design and baseline characteristics of the OMEGA study, which aims to contribute to the understanding of the natural history of GA. The OMEGA study will provide estimates of the ability to detect change and retest reliability for a panel of structure and functional assessments.

Subretinal Fluid Resolution and Visual Acuity in Patients with Neovascular Age-Related Macular Degeneration: A HARBOR Post Hoc Analysis

To determine the effect of subretinal fluid (SRF) resolution on visual acuity in patients with neovascular age-related macular degeneration (nAMD) from the HARBOR trial. Post hoc analysis of the HARBOR trial (a phase 3, double-masked, randomized, active treatment-controlled trial of ranibizumab conducted between July 2009 and August 2012 [NCT00891735]) was carried out from January 2020 to July2021. Treatment-naive patients with nAMD and active subfoveal choroidal neovascularization (N= 1097). Multiple intervention arms were pooled for this analysis if SRF was present at baseline and intraretinal fluid/SRF resolved during the study, based on spectral-domain OCT (n= 349). Three monthly loading doses followed by intravitreal injections of 0.5-mg or 2.0-mg ranibizumab were administered monthly or pro re nata over 24 months. Mean change in ETDRS best-corrected visual acuity (BCVA) between the month before SRF resolution and the month of SRF resolution detection. Visual outcomes at months 12 and 24 were analyzed in eyes without SRF recurrence after SRF resolution. The proportion of patients who lost ≤ 4 letters were considered as vision gainers/maintainers and those who lost ≥ 5 were considered as vision losers. Of 349 patients, 32 patients (9%) lost ≥ 5 ETDRS letters (mean [95% confidence interval (CI)], -9.9 letters [-12.0,-7.9]) and 317 (91%) of the eyes gained/maintained BCVA (mean, 6.1 letters [95% CI, 5.3, 6.8]) between the month before SRF resolution and the month of SRF resolution. There were no differences in baseline ocular characteristics between patient groups. Among eyes without SRF recurrence after SRF resolution (64%; 224/349), eyes that lost ≥ 5 ETDRS letters compared with those that gained/maintained letters at the time of SRF resolution had reduced visual outcome gains from baseline to month 12 (1.4 vs. 12.9 letters) and month 24 (0.0 vs. 12.6 letters). A greater proportion of ranibizumab-treated eyes with nAMD gained/maintained visual acuity at SRF resolution. Approximately 9% of eyes lost vision during SRF resolution; these eyes had reduced final visual acuity gains at 12 and 24 months. Further analyses are warranted to investigate potential underlying factors and discuss the treatment implications if confirmed.

Vitrectomy, subretinal Tissue plasminogen activator and Intravitreal Gas for submacular haemorrhage secondary to Exudative Age-Related macular degeneration (TIGER): study protocol for a phase 3, pan-European, two-group, non-commercial, active-control, observer-masked, superiority, randomised controlled surgical trial

BackgroundNeovascular (wet) age-related macular degeneration (AMD) can be associated with large submacular haemorrhage (SMH). The natural history of SMH is very poor, with typically marked and permanent loss of central vision in the affected eye. Practice surveys indicate varied management approaches including observation, intravitreal anti-vascular endothelial growth factor therapy, intravitreal gas to pneumatically displace SMH, intravitreal alteplase (tissue plasminogen activator, TPA) to dissolve the clot, subretinal TPA via vitrectomy, and varying combinations thereof. No large, published, randomised controlled trials have compared these management options.MethodsTIGER is a phase 3, pan-European, two-group, active-control, observer-masked, superiority, randomised controlled surgical trial. Eligible participants have large, fovea-involving SMH of no more than 15 days duration due to treatment-naïve or previously treated neovascular AMD, including idiopathic polypoidal choroidal vasculopathy and retinal angiomatous proliferation. A total of 210 participants are randomised in a 1:1 ratio to pars plana vitrectomy, off-label subretinal TPA up to 25 μg in 0.25 ml, intravitreal 20% sulfahexafluoride gas and intravitreal aflibercept, or intravitreal aflibercept monotherapy. Aflibercept 2 mg is administered to both groups monthly for 3 doses, then 2-monthly to month 12. The primary efficacy outcome is the proportion of participants with best-corrected visual acuity (BCVA) gain of ≥ 10 Early Treatment Diabetic Retinopathy (ETDRS) letters in the study eye at month 12. Secondary efficacy outcomes (at 6 and 12 months unless noted otherwise) are proportion of participants with a BCVA gain of ≥ 10 ETDRS letters at 6 months, mean ETDRS BCVA, Radner maximum reading speed, National Eye Institute 25-item Visual Function Questionnaire composite score, EQ-5D-5L with vision bolt-on score, Short Warwick and Edinburgh Mental Wellbeing score, scotoma size on Humphrey field analyser, and presence/absence of subfoveal fibrosis and/or atrophy and area of fibrosis/atrophy using independent reading centre multimodal image analysis (12 months only). Key safety outcomes are adverse events, serious adverse events, and important medical events, coded using the Medical Dictionary for Regulatory Activities Preferred Terms.DiscussionThe best management of SMH is unknown. TIGER aims to establish if the benefits of SMH surgery outweigh the risks, relative to aflibercept monotherapy.Trial registrationClinicalTrials.govNCT04663750; EudraCT: 2020-004917-10.

Defining inclusion criteria and endpoints for clinical trials: a prospective cross-sectional study in CRB1-associated retinal dystrophies.

PurposeTo investigate the retinal structure and function in patients with CRB1‐associated retinal dystrophies (RD) and to explore potential clinical endpoints.MethodsIn this prospective cross‐sectional study, 22 patients with genetically confirmed CRB1‐RD (aged 6–74 years), and who had a decimal best‐corrected visual acuity (BCVA) ≥ 0.05 at the last visit, were studied clinically with ETDRS BCVA, corneal topography, spectral‐domain optical coherence tomography (SD‐OCT), fundus autofluorescence, Goldmann visual field (VF), microperimetry, full‐field electroretinography (ERG) and full‐field stimulus testing (FST). Ten patients were from a genetic isolate (GI).ResultsPatients had retinitis pigmentosa (n = 19; GI and non‐GI), cone‐rod dystrophy (n = 2; GI) or macular dystrophy (n = 1; non‐GI). Median age at first symptom onset was 3 years (range 0.8–49). Median decimal BCVA in the better and worse‐seeing eye was 0.18 (range 0.05–0.83) and 0.08 (range light perception‐0.72), respectively. Spectral‐domain optical coherence tomography (SD‐OCT) showed cystoid maculopathy in 8 subjects; inner retinal thickening (n = 20), a well‐preserved (para)foveal outer retina (n = 7) or severe (para)foveal outer retinal atrophy (n = 14). All retinal layers were discernible in 13/21 patients (62%), with mild to moderate laminar disorganization in the others. Nanophthalmos was observed in 8 patients (36%). Full‐field stimulus testing (FST) provided a subjective outcome measure for retinal sensitivity in eyes with (nearly) extinguished ERG amplitudes.ConclusionsDespite the generally severe course of CRB1‐RDs, symptom onset and central visual function are variable, even at advanced ages. Phenotypes may vary within the same family. Imaging and functional studies in a prospective longitudinal setting should clarify which endpoints may be most appropriate in a clinical trial.

Pedicle internal limiting membrane flap technique for very large macular holes: a preliminary report

BackgroundConventional vitrectomy technique for macular hole surgery has a good outcome in small and medium macular holes, but for very large macular holes (minimum linear diameter higher than 700 μm) other techniques were developed aiming to achieve greater rates of closure and visual acuity gain. The purpose of this article is to report the anatomical and functional outcomes of four very large macular hole (MH) cases which have undergone vitrectomy with the pedicle internal limiting membrane (ILM) flap technique.MethodsThis is a retrospective series of four patients with large MH who were treated with vitrectomy and the pedicle ILM flap technique. Comprehensive ophthalmologic evaluation was performed before surgery and included ETDRS best-corrected visual acuity (BCVA) and spectral domain optical coherence tomography (SD-OCT) for MH measures: height, minimum linear diameter (MLD) and external base diameter. The particular detail of this technique is related to ILM flap creation. During the peeling, the ILM was not removed completely from the retina but was left attached to the edges of the macular hole and subsequently trimmed with the vitrectomy probe using the scissors mode.ResultsFour patients with very large MH underwent PPV and the pedicle ILM flap technique was used to pursue macular closure. Median preoperative BCVA was 20/400 (range: 20/320 to 20/400) and median postoperative BCVA was 20/200 (range: 20/320 to 20/200). Of the 4 cases reported, 3 obtained anatomical closure (75%), and also presented BCVA improvement after surgery, considering the last follow-up visit of each case. No additional procedures were performed in either case. One patient demonstrated no anatomic and functional improvement.ConclusionThe present study describes the first Brazilian case series of very large MH treated by the inverted pedicle ILM flap technique. This technique was associated with anatomic and visual improvement in most cases, and represents an alternative therapeutic approach for large macular holes.Trial Registration Project registered in Plataforma Brasil with CAAE number 30163520.0.0000.5440 and approved in ethics committee from Ribeirão Preto Medical School Clinics Hospital, University of São Paulo—Ribeirão Preto, São Paulo, Brazil (appreciation number 3.948.426 gave the approval).

Visual Acuity Variability: Comparing Discrepancies between Snellen and ETDRS Measurements among Subjects Entering Prospective Trials

To compare the variability between Snellen visual acuity (VA) and Early Treatment Diabetic Retinopathy (ETDRS) best-corrected VA (BCVA) measurements. Retrospective chart review. Eyes from subjects entering 12 prospective retinal trials in a large, urban retina practice. Eyes were included if a Snellen VA measurement was performed at the visit preceding trial screening and VA was better than counting fingers. Snellen VA and ETDRS BCVA were then converted to logarithm of the minimum angle of resolution (logMAR) units, and the variability between measurements was calculated. Outcome measures include VA variability among disease states, absolute VA, and central subfield thickness (CST). A total of 773 eyes of 413 subjects were identified with a mean of 27.2 days (median, 19; 95% confidence interval [CI], 25.1-29.3) between measurements. Mean Snellen and ETDRS measurements were 0.40 (20/50) and 0.27 logMAR (20/40), respectively. Overall, mean ETDRS BCVA was 6.1 letters better than Snellen VA (median, 5.8; 95% CI, 5.3-7.0; P < 0.05); 76.6% of eyes had improved ETDRS. Restricting the number of days between measurements did not result in any meaningful differences from this directionality. Among eyes with worse VA, variation was more pronounced than among eyes with better VA; eyes 20/25 or better were a mean+1.9 letters better on ETDRS testing (P < 0.05) and eyes 20/160 or worse were a mean+12.6 letters better on ETDRS testing (P < 0.05). Subgroup analyses by disease state found statistically significantly better vision measurements with the ETDRS protocol compared with Snellen in 4 of the 5 disease states studied. Although lens status did not affect the extent of discrepancy between ETDRS and Snellen measurements, amount of retinal edema (CST) did: increased CST correlated with increased variability. The ETDRS protocol BCVA measurement resulted in significantly better scores when compared with Snellen VA measurements. This difference was more pronounced among eyes with worse VA. Additionally, specific retinal disease states and anatomic variables such as extent of retinal edema (CST) may have a meaningful impact on the anticipated variability between ETDRS and Snellen VA measurement.

Réponse visuelle et anatomique en condition de « vraie vie » du traitement par aflibercept chez les patients naïfs atteints de dégénérescence maculaire liée à l’âge exsudative

The goal of this study was to evaluate the "real life" visual and anatomical outcomes of aflibercept treatment for treatment-naive patients with exudative AMD. This was a retrospective study of patients treated with aflibercept in the department of Ophthalmology at the University Hospital of Bordeaux between November 2013 and July 2015. The follow-up period varied from 3months to 2years. All patients received an induction phase with 3monthly intravitreal injections (IVT) followed by personalized monitoring. ETDRS best-corrected visual acuity (BCVA), fundus examination and OCT were performed at each visit. Data were collected at day 0, 3 months, 6, 9, 12months, 18 and 24months. Forty-three eyes of forty patients, mean age 77.7years, were included, with a minimum of 3months follow-up. Twenty-five eyes were followed for 1year; 5 eyes for two years. At baseline, the mean BCVA was 55.7 letters. Patients received 7.5 injections on average the first year and 2.6 the 2nd year. The mean gain of visual acuity was +7.3 letters at 3 months, +6.2 letters at 12 months, and +6.8 letters at 2years. Anatomically, the OCT data showed a decline of all parameters. The central macular thickness decreased by 118.3μm at 3months, 136.4μm at 12months and 65.5μm at 2years. Aflibercept can achieve effective visual and anatomical outcomes with results, which approach the pivotal studies, despite the use of personalized protocols and longer monitoring intervals.

Causes of visual impairment in patients with ocular toxoplasmosis

The aim of this study was to report the causes of visual impairment in patients with the classic clinical presentation of ocular toxoplasmosis (OT). Eight patients with OT underwent standardized ophthalmologic examination and fundus imaging. Macula and the lesions that could be visualized were evaluated by spectral domain optical coherence tomography (SOCT) at presentation. The scan acquisition protocols for SOCT included a radial line scan through the retinochoroiditis lesion, radial line macular scan, and horizontal volume scans at the macula. The mean age of the five (62.5%) women and three (37.5%) men was 25.7±7.6 years. The mean logMAR ETDRS best-corrected visual acuity was 0.45 (Snellen equivalent, 20/50). SOCT findings of macula were normal in seven patients, and one patient had decreased retinal thickness from a healed chorioretinitis at the fovea. Of eight patients, two had 3+ vitreous haze, four had 2+ vitreous haze, and two had 1+ vitreous haze at presentation. OCT scans revealed vitreous hyperreflective dots in all patients with different densities in different radial scans. Hyperreflective dots were denser in macular scans of eyes in which the active lesion was closer to the fovea. In this study, visual impairment in majority of the patients was found to be related to vitreous cells and flare. Dense vitritis on macula scans and visual impairment were seen in the patients who had an active lesion closer to the fovea. SOCT may provide objective data of the cellular load of the eyes with posterior segment inflammation.

Ranibizumab 0.3 mg for Persistent Diabetic Macular Edema After Recent, Frequent, and Chronic Bevacizumab: The ROTATE Trial.

To evaluate the safety and efficacy of 0.3 mg ranibizumab (Lucentis; Genentech, South San Francisco, CA) in eyes with persistent diabetic macular edema (DME) after recent, chronic, and frequent bevacizumab (Avastin; Genentech, South San Francisco, CA). Open-label, prospective study of 0.3 mg ranibizumab for eyes with persistent DME after bevacizumab. Thirty eyes randomized to a sustained group or a pro re nata (PRN) dosing group. The mean change in ETDRS best-corrected visual acuity from baseline to 1 year was +6.7 letters in the sustained group, +6.4 letters in the PRN group, and +6.5 letters overall. There was an overall mean reduction of 116 µm from baseline central subfield thickness at 1 year, with -92 µm and -127 µm decreases in the sustained and PRN groups, respectively. Adverse events included two deaths; one patient with multiple cardiopulmonary comorbidities, myocardial infarction, stroke, osteomyelitis; and mild posterior subcapsular cataracts in two eyes. Ranibizumab 0.3 mg demonstrated improved visual and anatomic outcomes in patients with persistent DME following bevacizumab. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:1030-1037.].

Selective retina therapy (SRT) for diabetes macular edema in Korean patients: 12‐months results

PurposeSelective Retina Therapy can induce proliferation and migration of retinal pigment epithelium (RPE) cells at SRT‐irradiated areas without damaging photoreceptor cells. We demonstrate 1‐year clinical results of SRT for clinically significant diabetic macular edema (DME) in Korean patients.MethodsProspective nonrandomized interventional case series study. Twenty‐three eyes of 21 patients with clinically significant DME were treated with SRT and followed up for 12 months. After analysis of the correlation between the RM value and FFA visibility, the sensitivity and specificity of reflectometry was calculated. We measured best‐corrected ETDRS visual acuity (BCVA). Microperimetry was employed to measure the macular sensitivity within the central 10° visual field, and the central macular thickness (CMT) and maximum macular thickness (MMT) were measured at every 3 months. Patients were considered for retreatment at 3 months if there was no decrease in CMT.ResultsThirteen of 23 eyes were included for the analysis of 1‐year results. BCVA improved from 69.5 letters at baseline to 76.23 letters at 6 months and 71.3 letters at 1 year. Although change in CMT did not demonstrate a significant change at two‐time points, MMT were decreased from 446.7 ± 78.4 μm to 423.5 ± 76.5 μm, 408.5 ± 59.6 at 6 months, 12 months (all p &lt; 0.05) and mean macular sensitivity were increased from 21.5 ± 3.1 dB to 22.9 ± 2.4 dB, 23.2 ± 2.5 dB respectively. (p = 0.009, p = 0.001). Additional SRT was performed for nine eyes (69.2%).ConclusionsIn 9 of 23 eyes (39.1%), BCVA was maintained or improved by SRT monotherapy during 1 year follow‐up period. The improvement in maximum macular thickness (MMT) and macular sensitivity support that SRT treatment could be effective and safe modality in Korean patients with clinically significant DME.

Half-Dose Verteporfin Photodynamic Therapy (hdPDT) in the Treatment of Central Serous Chorioretinopathy

To estimate the efficacy and safety profile of half-dose photodynamic therapy (hdPDT) for treating central serous chorioretinopathy (CSC). An interventional, retrospective case series of patients with CSC (symptoms ≧ 3 months) receiving half-dose PDT (3 mg/m2 verteporfin). The ophthalmic examination at baseline and at 8 and 16 weeks after treatment included slit-lamp biomicroscopy, indirect ophthalmoscopy, measurement of intraocular pressure (IOP), ETDRS best-corrected visual acuity (BCVA), Amsler grid screening and contrast visual acuity (CVA). Fluorescein angiography (FA), autofluorescence (FAF) and optical coherence tomography (OCT) were measured at each visit. Central macular thickness (CMT) was measured automatically. 12 eyes of 12 patients (10 male and 2 female patients; mean age 46.6 ± 7.91 years) were included in this study. Anatomical resolution was obtained in 10 eyes (83.4 %) at week 16, but 2 eyes (16.6 %) exhibited persistent SRD throughout the follow-up period. Baseline CMT decreased from initially 330.1 µm ± 131.3 to 205.6 µm ± 97.6 (p = 0.034) at week 8 and to 220.3 µm ± 120.1 (p = 0.05) at week 16. Visual acuity (number of total letters read) significantly improved from initially 82.8 ± 11.5 to 86.8 ± 13.9 at week 8 and 91.3 ± 13.8 at week 16 (p = 0.012). Contrast visual acuity (calculated decimal visual acuity) significantly improved from initially 0.14 ± 0.09 to 0.38 ± 0.28 (p = 0.002) at week 16. After therapy, no significant changes in RPE could be detected with FAF and no ocular adverse events were observed. PDT with half-dose verteporfin resulted in reduced leakage in FA, enhanced visual acuity and resolution of subretinal fluid in OCT in patients with CSC, with no detected side effects of treatment.

Intérêt de la photothérapie dynamique dans les choriorétinopathies séreuses centrales chroniques et les épithéliopathies rétiniennes diffuses exsudatives

To report outcomes in patients with long-standing (more than 6 months) chronic central serous chorioretinopathy (CSC) treated with low-fluence Visudyne(®) photodynamic therapy (LFV-PDT). The clinical, angiographic and optical coherence tomography (OCT) results of patients with long-standing chronic central serous chorioretinopathy (CCSC) treated with LFV-PDT in the Lyon Centre Rabelais between 2002 and 2008 were retrospectively analyzed. A comprehensive check-up (macular syndrome signs, ETDRS best-corrected visual acuity [BCVA], biomicroscopy, fluorescein [FA] and indocyanine green [ICGA] angiographies, OCT scans) was performed before LFV-PDT treatment and 3 months later. Patients were then followed regularly and retreated in case of recurrence. The LFV-PDT treatment, with a fluence of 25 J/cm(2) at an irradiance of 300 mW, was guided by ICGA. Forty-one eyes of 34 patients (27 males; mean age: 53 years) were included, of which 18 eyes had already been treated with laser photocoagulation. Several leaking points were visible on FA in most of the cases (n=38), mainly in the macula (35 cases). Before treatment, metamorphopsia was noted in 51% of the cases, intraretinal edema (IRE) was present on OCT scans in 71%, serous retinal detachment (SRD) in 85%, and pigment epithelial detachment (PED) in 10%. Thirty-nine eyes had only one treatment session and one eye was retreated once. At 3 months after LFV-PDT, IRE was present in 15% of the cases, SRD in 12%, and PED in 2%. At the end of the 20-month follow-up, IRE was present in 14% of the cases, SRD in 15%, and PED in 0%. Macular atrophy was observed on OCT in most of the cases at the end of the follow-up (mean central thickness, 144.5 μm). Compared to the initial BCVA, at 3 months after LFV-PDT, BCVA decreased in 22% of the cases, stabilized in 39%, and increased in 39%, while at the end of the follow-up, BCVA decreased in 12% of the cases, stabilized in 17%, and increased in 71%. No complication was observed. LFV-PDT treatment for patients with long-standing chronic central serous chorioretinopathy results in anatomical and functional improvement (sustained disappearance of the exudative phenomenon in most cases and increased BCVA in more than two-thirds of the cases). The macular atrophy observed may be due to the treatment or the natural course of the disease.

Age-Related Macular Degeneration and Risk Factors for the Development of Choroidal Neovascularisation in the Fellow Eye: A 3-Year Follow-Up Study

Introduction: The presence of large-sized drusen (≧125 µm), soft indistinct drusen, pigmentary changes, a large area of drusen and a choroidal neovascular membrane in one eye have been found to be predictive risk factors of late exudative age-related macular degeneration (AMD). Multimodal imaging potentially increases the possibility of indentifying further potential risk factors of developing wet AMD. Purpose: To identify morphological and/or functional baseline risk factors for the development of choroidal neovascularization (CNV) in a multimodal set of images from fellow eyes of patients with exudative AMD. Methods: Single-center, prospective, observational, longitudinal 2-year plus 1-year extension study of 62 patients with neovascular AMD in one eye (the nonstudy eye) and early age-related maculopathy (ARM) in the fellow eye (study eye). Best-corrected ETDRS visual acuity, fluorescein angiography (FA) and indocyanine green angiography (ICG), fundus photography, retinal leakage analysis, fundus autofluorescence imaging and optical coherence tomography (OCT Stratus 4.0.2, Carl Zeiss Meditech Inc.) were performed at baseline and every 6 months in order to identify both conversion to CNV as well as possible predictive features present before conversion. A semiautomated computer-assisted grading system was used for classifying fundus color images. Only eyes with 3 years of follow-up were considered for statistical analysis. Results: Fifty-two patients completed the 3-year study follow-up: 26 men and 26 women aged from 56 to 92 years (mean ± SD: 76 ± 6 years). CNV confirmed with FA developed in 46% of the 52 study eyes during the 3-year follow-up (24 converted eyes: 7 in the first year, 11 in the second and 6 in the third). A significantly higher risk for conversion to wet AMD was found only for leakage on a retinal leakage analyzer (odds ratio, OR = 5.0; 95% confidence interval, CI = 1.5–16.4; p = 0.006) detected at least in one visit before the onset of exudative lesions, for baseline ICG hot spots (OR = 7.2; 95% CI = 2.0–25.7; p = 0.002), baseline late ICG hot spots (OR = 4.7; 95% CI = 1.4–15.4; p = 0.009) and baseline early ICG hypofluorescent spots (OR = 3.7; 95% CI = 1.2–12.1; p = 0.025). The total area of drusen, the area of drusen in subfield 1, inner circle or outer circle, the total number of drusen and the number of drusen ≧125 µm, fundus autofluorescence patterns, OCT findings and the severity of ARM at baseline did not show any correlation with an increased risk of conversion to wet AMD. Conclusion: At 3 years, progression from early to late exudative AMD was superior to the expected rate (44%). ICG early and late hyperfluorescent spots or areas, ICG early hypofluorescent spots or areas and early leakage detected with the retinal leakage analyzer, but not pigmentary changes, large drusen, number and area of drusen at any location or a greater severity of ARM at baseline, showed to be a predictive parameter of conversion to wet AMD.

Intravitreal Injection of Commercially Available Ketorolac Tromethamine in Eyes with Diabetic Macular Edema Refractory to Laser Photocoagulation

Purpose: To evaluate the short-term effect of a single intravitreal injection of commercially available ketorolac tromethamine (KT) in eyes with diabetic macular edema refractory to laser photocoagulation.Methods: Prospective interventional case series. Twenty five patients with diabetic macular edema refractory to laser photocoagulation received a single intravitreal injection of commercially available KT (Toradol®), in a dose of 3000 µg. Examination included assessment of ETDRS-best corrected visual acuity (BCVA), measurement of intraocular pressure and high resolution imaging by optical coherence tomography, preoperatively and 7, 15, and 30 days postoperatively.Results: In the follow up visits at 7, 15 and 30 days, BCVA had improved five or more letters in 20% (95% confidence interval, 7.7–38.9%), 16% (95% confidence interval, 5.3–34.2%) and 28% (95% confidence interval, 13.2–47.7%) respectively. An improvement in macular thickness was also observed, although it has not been statistically significant.Conclusion: This pilot study showed that a single intravitreal injection of 3000 µg of commercial KT led to a short-term improvement of visual acuity in approximately 30% of eyes with diabetic macular edema refractory to laser photocoagulation.

Selective retina therapy (SRT) for clinically significant diabetic macular edema

To test selective retina therapy (SRT) as a treatment of clinically significant diabetic macular edema (DME). Prospective two-center interventional uncontrolled phase II pilot study. Thirty-nine eyes of 39 patients with previously untreated non-ischemic DME were treated with focal laser treatment using a Q-switched frequency doubled Nd:YLF laser which selectively affects the retinal pigment epithelium while sparing the photoreceptor layer. Optoacoustic measurements, fundus fluorescein angiography (FFA), and funduscopy were used to determine the individual threshold of RPE damage of each patient. The pulse energy was adjusted to apply angiographically visible but funduscopically invisible effects. Optoacoustic measurements were correlated with funduscopy and FFA. Follow-up examinations at 3 and 6 months post-treatment included best-corrected ETDRS visual acuity (BCVA), FFA, fundus photography, and retinal thickness measured by optical coherence tomography. The primary outcome measure was change of BCVA. Other outcome measures were change of retinal thickness, presence of hard exudates, leakage in FFA, accuracy of optoacoustic measurements, and correlation of BCVA with change of anatomical and systemic parameters. Mean BCVA improved from 43.7 letters (standard deviation, SD=9.1) at baseline to 46.1 letters (SD=10.5) at the 6-month follow-up (p=0.02). BCVA improved (>5 letters) or remained stable (+/-5 letters) in 84% of eyes. Thirteen percent of eyes improved by > or =10 letters, while 16% of eyes lost more than 5 letters. There was no severe loss of vision (> or =15 letters). Overall, retinal thickness, hard exudates, and leakage in FFA did not change significantly (p> 0.05), while improvement of BCVA correlated with a reduction of hard exudates (p=0.01) and central retinal thickness (p=0.01). Specificity and sensitivity of detecting the angiographic visible threshold of RPE damage by optoacoustic measurements were 86% and 70% respectively. No adverse effects or pain were noted during or after treatment. Conclusions Functional and anatomical improvement or stabilization was observed in most patients. SRT appears to be safe. Optoacoustic measurements accurately detect the individual threshold of RPE damage. A randomized trial is required to further test efficacy and safety of SRT as a treatment of clinically significant diabetic macular edema (DME).

Choroidal Neovascularization in Pathologic Myopia: Intravitreal Ranibizumab Versus Bevacizumab—A Randomized Controlled Trial

To compare the short-term efficacy and safety of intravitreal ranibizumab versus bevacizumab in treating myopic choroidal neovascularization (CNV). Prospective, comparative, randomized, interventional study. Thirty-two eyes from 32 patients with myopic CNV were consecutively enrolled and randomly treated, in a 1:1 ratio, with intravitreal ranibizumab (0.5 mg) or bevacizumab (1.25 mg) as needed, after the first injection. ETDRS best-corrected visual acuity (BCVA), foveal center thickness (FCT) on optical coherence tomography (OCT), and fluorescein angiographic findings were examined before and after treatment. Patients were followed up for 6 months. No statistically significant difference in the BCVA improvement, as well as in the FCT reduction, was found between groups during follow-up (P value at 1, 3, 6 months > .05). Complete resolution of fluorescein leakage was observed in all 16 bevacizumab-treated eyes and in 15 out of 16 (93.7%) ranibizumab-treated eyes. No ocular or systemic adverse effects from treatment were encountered. This randomized clinical study cannot determine a statistically significant difference in anti-VEGF treatment effect between ranibizumab and bevacizumab for the treatment of CNV secondary to pathologic myopia. A larger study is required to determine the relative efficacy and duration of action of these drugs.