Center Point Thickness Research Articles

Interim Results of the Phase III Portal Extension Trial of the Port Delivery System with Ranibizumab in Neovascular Age-Related Macular Degeneration

ObjectiveThe Port Delivery System with ranibizumab (PDS) is approved in the United States for neovascular age-related macular degeneration (nAMD). Portal (NCT03683251) is evaluating long-term safety and tolerability of the PDS in patients with nAMD who completed the phase II Ladder (NCT02510794) or phase III Archway (NCT03677934) trials. DesignMulticenter, nonrandomized, open-label, extension clinical trial. ParticipantsAll-PDS safety population (N = 555) comprises patients enrolled in Portal who completed Ladder or Archway. Due to data availability, efficacy population comprises Ladder-to-Portal patients only: patients who previously received PDS 10, 40, or 100 mg/ml pro re nata (as-needed [PRN]; n = 58, 62, 59, respectively) or monthly intravitreal ranibizumab 0.5-mg injections (monthly ranibizumab; n = 41) in Ladder and subsequently enrolled in Portal. MethodsLadder patients received PDS refill-exchanges PRN or monthly ranibizumab. Archway patients received PDS 100 mg/ml with fixed refill-exchanges every 24 weeks (PDS Q24W) or monthly ranibizumab. Once enrolled in Portal, all patients receive PDS Q24W from day 1. Main Outcome MeasuresOcular adverse events of special interest (AESIs); changes from baseline in best-corrected visual acuity (BCVA) and center point thickness (CPT); supplemental ranibizumab treatment between refill-exchange procedures; PDS Patient Preference Questionnaire results. ResultsIn the All-PDS safety population (mean follow-up, 111 weeks), 137 (24.7%) patients had ≥ 1 ocular AESI; most common were cataract (11.4%), vitreous hemorrhage (6.1%), conjunctival thickening (bleb)/filtering bleb leak (6.3%). Endophthalmitis occurred in 11 of 555 (2.0%) patients. For Ladder-to-Portal patients previously treated with PDS 100 mg/ml or monthly ranibizumab, BCVA remained stable from baseline to month 48; mean (95% confidence interval) changes from baseline were 0.1 (−6.6, 6.8; n = 31) and 2.3 (−9.4, 14.1; n = 15) letters, respectively; CPT remained stable through month 48. Approximately 95% of patients did not need supplemental treatment before each refill-exchange for > 2 years since Portal enrollment. Of Ladder-to-Portal previous monthly ranibizumab patients, 92% preferred the PDS over injections. ConclusionsInterim results from Portal suggest 4-year maintenance of visual/anatomic outcomes with PDS 100 mg/ml, with the PDS preferred to monthly injections. Long-term safety profile of the PDS is well characterized.

Prognostic impact of hyperreflective foci in nonsyndromic retinitis pigmentosa

PurposeTo evaluate the prognostic impact of hyperreflective foci (HRF) on spectral-domain optical coherence tomography (SD-OCT) in nonsyndromic retinitis pigmentosa (RP).MethodsRetrospective, single-center cohort study including genetically-tested RP patients with a minimum follow-up of 24 months. Clinical data including demographics, genetic results and best-corrected visual acuity (BCVA) at baseline and follow-up were collected. Horizontal and vertical SD-OCT scans were analyzed by 2 independent graders. Outer nuclear layer (ONL) thickness and ellipsoid zone (EZ) width were manually measured in horizontal and vertical scans. HRF were classified according to location: outer retinal layers within the central 3mm (central-HRF), outer retinal layers beyond the central 3mm (perifoveal-HRF), and choroid (choroidal-HRF). Central macular thickness (CMT), central point thickness (CPT) and choroidal thickness (CT) at baseline and follow-up were also recorded.ResultsA total of 175 eyes from 94 RP patients (47.9% female, mean age 50.7±15.5 years) were included, with a mean follow-up of 29.24±7.17 months. Mean ETDRS (early treatment diabetic retinopathy study) BCVA decreased from 61.09±23.54 to 56.09±26.65 (p=0.082). At baseline, 72 eyes (41.1%) showed central-HRF, 110 eyes (62.9%) had perifoveal-HRF and 149 eyes (85.1%) exhibited choroidal-HRF. Central-HRF and perifoveal-HRF were associated with worse final BCVA, as well as greater BCVA deterioration (all p<0.0029). Only central-HRF were associated with a worse final CMT (p<0.001). Shorter EZ widths were associated with all types of HRF (p<0.05). Perifoveal and choroidal-HRF predicted smaller final EZ areas (p<0.01).ConclusionHRF are highly prevalent in RP patients and appear to have a negative prognostic impact in visual function and EZ area.

Foveal Microstructure and Visual Outcomes after Pars Plana Vitrectomy in Patients with Different Types of Epiretinal Membrane Foveoschisis

Introduction: The aim of this study was to evaluate the clinical characteristics and surgical outcomes of the epiretinal membrane foveoschisis (ERM-FS) with different morphological types. Methods: This retrospective observational study reviewed 44 consecutive ERM-FS patients who underwent ERM surgery. According to the optical coherence tomography images, ERM-FS was classified into three groups: group A, FS crossed the fovea with the foveola elevated; group B, FS located at the foveal edges with a near-normal central foveal point thickness; and group C, FS with undermined foveal edges with a near-normal central foveal point thickness. Results: There were 10 eyes in group A, 20 eyes in group B, and 14 eyes in group C. Preoperatively, eyes in group A had the best best-corrected visual acuity (BCVA), the thickest central foveal point thickness, and the highest ellipsoid zone (EZ) intact rate among the three groups. After surgery, a resolution of foveoschisis was observed in 40.0%, 45.0%, and 50.0% of the eyes in group A, group B, and group C (p = 0.928), respectively. BCVA was significantly improved postoperatively. Although there was no significant difference in BCVA among the three groups at 1 month postoperatively, BCVA of group A was the best at 4 and 10 months. Correlation analysis indicated that the type of ERM-FS, baseline BCVA, central foveal point thickness, and postoperative EZ continuity (all p < 0.05) were important factors for the final BCVA. Conclusions: The damage to the retinal structure and visual function was milder in group A ERM-FS. Our study emphasized the necessity of OCT-based subtyping in patients with ERM-FS.

Performance of retinal fluid monitoring in OCT imaging by automated deep learning versus human expert grading in neovascular AMD

PurposeTo evaluate the reliability of automated fluid detection in identifying retinal fluid activity in OCT scans of patients treated with anti-VEGF therapy for neovascular age-related macular degeneration by correlating human expert and automated measurements with central retinal subfield thickness (CSFT) and fluid volume values.MethodsWe utilized an automated deep learning approach to quantify macular fluid in SD-OCT volumes (Cirrus, Spectralis, Topcon) from patients of HAWK and HARRIER Studies. Three-dimensional volumes for IRF and SRF were measured at baseline and under therapy in the central millimeter and compared to fluid gradings, CSFT and foveal centerpoint thickness (CPT) values measured by the Vienna Reading Center.Results41.906 SD-OCT volume scans were included into the analysis. Concordance between human expert grading and automated algorithm performance reached AUC values of 0.93/0.85 for IRF and 0.87 for SRF in HARRIER/HAWK in the central millimeter. IRF volumes showed a moderate correlation with CSFT at baseline (HAWK: r = 0.54; HARRIER: r = 0.62) and weaker correlation under therapy (HAWK: r = 0.44; HARRIER: r = 0.34). SRF and CSFT correlations were low at baseline (HAWK: r = 0.29; HARRIER: r = 0.22) and under therapy (HAWK: r = 0.38; HARRIER: r = 0.45). The residual standard error (IRF: 75.90 µm; SRF: 95.26 µm) and marginal residual standard deviations (IRF: 46.35 µm; SRF: 44.19 µm) of fluid volume were high compared to the range of CSFT values.ConclusionDeep learning-based segmentation of retinal fluid performs reliably on OCT images. CSFT values are weak indicators for fluid activity in nAMD. Automated quantification of fluid types, highlight the potential of deep learning-based approaches to objectively monitor anti-VEGF therapy.

Morphological Characteristics of Foveal Pit Base and Its Impact on Visual Acuity in Macular Pseudoholes

Introduction: To investigate the characteristics of macular pseudoholes (MPHs) with different foveal profiles and their impact on preoperative and postoperative visual acuity (VA). Methods: A retrospective review of 47 eyes from 46 consecutive patients with MPH who had undergone vitrectomy was conducted. The MPHs were classified into u-shape and v-shape according to the morphological description of the foveola base. The best-corrected visual acuity (BCVA), central foveal point thickness, parafoveal thickness, parafoveal inner and outer retinal thickness, stretched lamellar cleavage, microcystic macular edema (MME), disorganization of retinal inner layers (DRIL), and the integrity of outer retinal layers were recorded. Results: The eyes in the v-shaped group (n = 31) had lower BCVA, thicker retinal thickness, more intraretinal cleavage, MME, and DRIL than the u-shaped (n = 16) group (all p < 0.05). Multiple regression analysis revealed that the morphology of the foveola base was significantly related to the preoperative BCVA (p = 0.025). The VA was significantly improved in both groups, and the improvement was greater in the v-shaped group (p = 0.024). No significant difference was found in the postoperative BCVA between the two groups (all p > 0.05). Conclusion: The v-shape, reflecting the stretch in the foveola, had a significant impact on preoperative BCVA. However, the VA was improved after surgery whatever their initial foveal profile.

Hyper- and hypo-perfusion of choriocapillaris in the eyes with pachychoroid pigment epitheliopathy.

To evaluate the changes in choriocapillaris vessel density (VD) in eyes with pachychoroid pigment epitheliopathy (PPE) using swept-source optical coherence tomography (OCT) angiography (OCTA). This study included 83 eyes with PPE and 42 control eyes. We collected OCT and OCTA parameters, including central point thickness, subfoveal choroidal thickness (SFChT), and choriocapillaris VD of the fovea (CC fovea) and parafovea. The parafoveal area was divided into superior, nasal, inferior, and temporal choriocapillaris areas. Maximum (CC max) and minimum (CC min) choriocapillaris VD were defined as the highest and lowest values among the four parafoveal subfield VDs, respectively. We analyzed the average choriocapillaris VD, CC max, CC min, CC fovea, and the difference between CC max and CC min (CC delta) individually and compared all the parameters between PPE and control eyes. CC max (56.0% ± 1.7%) was significantly higher and CC min (50.9% ± 2.0%) significantly lower in eyes with PPE than in control eyes (CC max, 55.3% ± 1.0%, P = 0.006; CC min, 51.5% ± 1.3%, P = 0.046). The CC delta value (5.0% ± 2.1%) and SFChT (389.9 ± 129.9μm) were also significantly higher in eyes with PPE than in the control group (3.7% ± 1.5%, P < 0.001; 268.2 ± 102.2μm, P < 0.001; respectively). Choriocapillaris VD showed higher variability (hyperperfusion and hypoperfusion) in eyes with PPE than in control eyes. Choriocapillaris hypoperfusion may precede the development of PPE; however, choriocapillaris hyperperfusion is associated with projection artifacts.

Efficacy and safety of intravitreal HLX04-O, an anti-VEGF monoclonal antibody, for the treatment of wet age-related macular degeneration.

To evaluate the efficacy and safety of HLX04-O, an investigational ophthalmic formulation of HLX04 (bevacizumab biosimilar) for intravitreal injection, as a treatment for wet age-related macular degeneration (wAMD) in a phase 1/2 clinical trial (NCT04993352). Eligible patients with wAMD were enrolled to receive HLX04-O intravitreal injections at a dose of 1.25 mg/0.05 mL every four weeks. Efficacy and adverse events were evaluated every month during study visits. A 76-year-old male with wAMD in his left eye participated in the trial and completed six cycles of HLX04-O intravitreal injections. Changes were observed in macular center point thickness (baseline vs last study visit, 437 vs 255 µm) and best-corrected visual acuity letter score (baseline vs last study visit, 36 vs 77) of the affected eye, which indicated an improvement in wAMD over treatment. No adverse events were reported by the data cutoff date. HLX04-O at 1.25 mg/0.05 mL every four weeks is well tolerated in this patient, demonstrating promising safety and efficacy in wAMD treatment. Large-scale studies are required to confirm the outcomes.

Influence of the Size of the Foveal Avascular Zone on Functional and Morphological Parameters in Patients with Early-Stage Diabetic Retinopathy.

PurposeTo correlate functional and morphological parameters with foveal avascular zone’s (FAZ) size in diabetic patients with mild to moderate stage nonproliferative diabetic retinopathy.MethodsMonocentric and prospective study of a consecutive case series of diabetic patients. Medical history, best corrected visual acuity (BCVA), best corrected high/low contrast visual acuity (BChcVA/BClcVA), mean sensitivity (MS) and mean defect (MD) in central visual field testing, and FAZ size in fluorescein-angiography (FAG) were recorded. Macular thickness (central point thickness CPT, central subfield thickness CST) and volume measurements (central subfield volume CSV, total macular volume) were taken from SD-OCT (6x6mm ETDRS-grid). Groups were categorised as presenting FAZ sizes smaller (G1) or larger (G2) than 0.35mm2. Smallest (Q1) and largest quartiles (Q3) were also compared.ResultsThirty-six of 40 patients were included. MS differed significantly between G1 (n = 6) and G2 (n = 30), and BChcVA/BClcVA as well as TMV correlated significantly with FAZ size in correlation analysis. Mean HbA1c tended to be lower in G1 than G2. Patients in G1 were slightly older than in G2. Treatment period with insulin was shorter in G1/Q1 than in G2/Q3. CPT and TMV were lower in G1/Q1 than in G2/Q3. Our analysis of the FAZ in terms of patient age, HbA1c, disease duration and insulin therapy duration revealed no significance. That lack of significance also applies to BCVA, MS, MD, CPT, CST and CSV.ConclusionAs significantly associated, contrast sensitivity, central visual field parameters and potentially retinal thickness or volume seem to be suitable to detect early macular ischaemia. However, we failed to establish any correlation between FAZ and BCVA.

Vitreous cytokine levels following the administration of a single 0.19 mg fluocinolone acetonide (ILUVIEN®) implant in patients with refractory diabetic macular edema (DME)—results from the ILUVIT study

PurposeTo investigate the changes in vitreous inflammatory and angiogenic cytokine levels, primarily interleukin-(IL)-6, following intravitreal injection of the 0.19 mg fluocinolone acetonide (FAc, ILUVIEN®) implant in patients with diabetic macular edema.MethodsA single-center phase IV study involving 12 patients’ eyes with diabetic macular edema. Vitreous fluid samples were obtained prior to intravitreal injection of the fluocinolone acetonide implant and then again over a 6-month period. Vitreous samples were examined using a cytometric bead array to measure IL-6, IL-8, IP-10, MCP-1, VEGF, and CD54. PIGF and PEDF were measured using an enzyme-linked immunosorbent assay. Changes in the cytokine and chemokine expression patterns were analyzed. Clinical parameters such as BCVA and center point thickness (CPT) were also examined.ResultsThere were mean reductions in all parameters between baseline and month 6. Significant changes (p < 0.05 versus baseline) were observed in the expression of IL-6, IP-10, MCP-1, and CD54 following the administration of fluocinolone acetonide implant. VEGF and PIGF increased at month 1 before declining at month 6, though this trend was not significant. CPT decreased rapidly between screening and the first follow-up visit, and this decrease was sustained. BCVA remained relatively stable throughout.ConclusionThis study demonstrated changes in vitreous inflammatory and angiogenic cytokine levels following intravitreal injection of the FAc implant in patients with diabetic macular edema. Data show that the fluocinolone acetonide implant led to rapid and sustained reductions of some inflammatory cytokines with improvement of the overall clinical picture.

Baseline retinal thickness measurements with a novel integrated imaging system (concurrent optical coherence tomography and fundus photography) positively correlates with spectralis optical coherence tomography.

Traditionally fundus photographs and optical coherence tomography (OCT) are obtained separately during evaluation of retinal pathology. We describe a novel integrated imaging system (Monaco, Optos) that records both OCT as well as fundus photography concurrently. The present study aims to measure retinal thickness and compare it to OCT obtained with traditional spectral domain OCT in subjects without known retinal disease to establish normative data for clinical use. In this cross sectional study, fundus photographs and OCT was obtained concurrently in 34 eyes in healthy patients without any known retinal disease with integrated imaging system. OCT with spectralis was also obtained at the same visit for comparison. All subjects underwent a complete ophthalmologic exam to ensure the absence of ocular pathology. OCT was performed by the same operator. Central subfield thickness (CST), central point thickness (CPT), and retinal thickness in nine central subfields were measured with both 1 instruments. Fundus photographs were obtained. Students t-test was used to determine statistical significance. The mean CST as measured with MIIS-SD OCT and Spectralis OCT was 300.53±22.81 µm and 265.18±17.33 µm (P<0.001) respectively. The Pearson's correlation coefficient, r value was 0.5285, P<0.0013. The mean CPT as measured with MIIS-SD OCT and Spectralis OCT was 268.55±20.70 and 230.67±17.75 µm (P<0.001) respectively. The r-value was 0.5697, P<0.0004. The mean difference between retinal thicknesses was 44.88 µm (range, 21-91 µm) in the eight ETDRS subfields, with r value 0.53, P<0.05, ranging from 0.51 to 0.60. Concurrently obtained ultrawide angle fundus photographs revealed (200°) clear media, normal disc, normal vasculature and normal periphery in all patients with excellent resolution. Retinal thickness measurements strongly correlated with those obtained by Spectralis. An increased measurement in thickness of 35.35 µm was noted in the central fovea. In addition, wide-angle fundus photography was successfully obtained in all subjects. Integrated system provides quality fundus photographs as well as OCT, obviates the need for two separate instruments and likely improves the clinic flow.

Brolucizumab: Evaluation of Compassionate Use of a Complex Anti-VEGF Therapy.

ObjectiveTo report a consecutive series of compassionate, off-label use of intravitreal brolucizumab as a rescue therapy for complex, non-responsive macular edema. This report delineates primary diagnosis, indications for treatment, adverse events, and visual and anatomic outcomes after intravitreal brolucizumab.MethodsA retrospective review of a consecutive clinical case series of 110 eyes treated with intravitreal brolucizumab between January 1st and March 1st. 2020. All patients were included if they received intravitreal brolucizumab in an off-label delivery and had ongoing macular edema in the setting of prior, multiple intravitreal anti-VEGF and/or intravitreal triamcinolone acetonide. All patients had spectral domain OCT documented before, at the time of, and in serial follow-up after intravitreal brolucizumab.ResultsNinety-eight of 98 patients had marked decrease in macular edema. Indications for treatment were assigned to the primary etiologic diagnosis leading to the macular edema secondary to radiation retinopathy, complex epiretinal membrane, or complex diabetic retinopathy. In this series, sdOCT central point thickness decreased by an average of 71.5 microns, subretinal fluid resolved, and visual acuity was improved in 40% (greater than two Snellen lines) and stable in 60% (within two Snellen lines). No patient experienced a severe adverse event to specifically include vitritis and/or vasculitis.ConclusionIn this series, brolucizumab intravitreal injection was associated with significant improvement in macular edema in each diagnostic category. No serious complications to treatment were found in this series. Brolucizumab, though associated with known intraocular inflammation and vasculitis, demonstrated marked benefit in these complex eyes previously unresponsive to aggressive intravitreal pharmacotherapy.

Management of optic disc pit-associated maculopathy: A case series from a tertiary referral center.

To report outcomes of pars plana vitrectomy (PPV) combined with internal limiting membrane (ILM) stuffing technique in patients with optic disc pit associated maculopathy (ODP-M). Data including best-corrected visual acuity (BCVA), central macular thickness (CMT), foveal center point thickness (FCP), and maximum height of fluid (max_fluid) (intraretinal or subretinal) were collected from the medical records of the patients. Six eyes of six patients with a mean age of 28.0 ± 17.68 years (range: 9-53 year) underwent PPV + ILM plug surgery. The mean follow-up duration was 25.62 ± 26.11 months (range: 11.80-78.00 month) duration. The mean BCVA increased from 1.25 ± 1.04 logMAR (20/355, Snellen equivalent) to 0.86 ± 1.09 logMAR (20/144, Snellen equivalent) at last follow-up (p = 0.043). Compared to baseline, CMT, FCP, and max_fluid significantly decreased at all visits after the surgery (p < 0.05 for all visits). At last follow-up, 66.6% of the eyes (four eyes) showed complete resolution of fluid at a mean of 5.25 ± 4.99 months (range: 1-12 months) after the surgery. PPV with ILM plug seemed to be an effective surgical technique in ODP-M. Studies with longer follow-up and higher number of patients are needed to confirm our results.

Disorganization of the retinal inner layers as a predictor of visual acuity in eyes with macular edema secondary to uveitis.

To assess the correlation between disorganization of the retinal inner layers (DRIL) and best-corrected visual acuity (BCVA) in patients with uveitis and macular edema (UME) who underwent systemic treatment using optical coherence tomography (OCT). A retrospective clinical study of 23 patients (30 eyes) with DRIL and 23 patients (31 eyes) without DRIL secondary to UME were included. All patients underwent comprehensive ophthalmic examinations at baseline, 3, 6, and 12mo after local and systemic treatment. The OCT-based parameters included foveal center point thickness (FCPT), mean thickness (MT), and diameters of DRIL in horizontal and vertical directions. BCVA and OCT-based parameters were compared between the two groups. The relationship between each OCT parameter and BCVA was evaluated using linear correlation and regression analysis. At the initial visit, the mean baseline FCPT was 441.03±128.68 µm in the eyes with DRIL and 337.26±99.31 µm in the eyes without DRIL (P=0.001). No significant differences were observed in MT (P=0.357). The mean size of transverse and vertical diameters of DRIL was 684.07±267.51 and 267.07±104.61 µm at baseline, respectively. There was significant improvement in BCVA and OCT-based parameters at 3, 6, and 12mo in all cases (P<0.001 for each timepoint). In addition, significant differences were detected in BCVA and OCT parameters between eyes with and without DRIL at each time point (P<0.01 for each timepoint). A greater DRIL range at baseline was associated with a worse baseline BCVA (transverse diameter of DRIL: r=0.875, P<0.001; vertical diameter of DRIL: r=0.622, P<0.001). The transverse diameter of baseline DRIL was found to be significantly correlated with the final BCVA (P=0.003). The improvement in BCVA is associated with DRIL in patients with UME. DRIL is an easy-to-determine and robust imaging biomarker that could help predict BCVA prognosis in eyes with UME.

Association between early and late response in eyes with central or hemiretinal vein occlusion treated with anti-VEGF agents : SCORE2 report 12: secondary analysis of the SCORE2 clinical trial.

To assess whether early visual acuity letter score change from baseline (ΔVALS) and early spectral domain optical coherence tomography (SD-OCT) measures of center point thickness (CPT) are associated with later ΔVALS in eyes with macular edema due to central or hemiretinal vein occlusion treated with intravitreal aflibercept or bevacizumab. Secondary analysis of a randomized clinical trial of 362 participants. Considered separately at month 3, CPT (categorized as ≤ 300μm, > 300μm) and ΔVALS (categorized as < 5, 5-9, ≥ 10) are predictive of ΔVALS at month 6 (aflibercept: P = 0.02 for CPT and P < 0.0001 for ΔVALS; bevacizumab: P = 0.007 for CPT and P < 0.0001 for ΔVALS) and, except for CPT in thebevacizumabarm, also predictive of ΔVALS at month 12 (aflibercept: P = 0.03 for CPT and P < 0.0001 for ΔVALS; bevacizumab: P = 0.18 for CPT and P < 0.0001 for ΔVALS). Month 3 predictors are also associated with average ΔVALS from months 4 to 12 (CPT P = 0.01 in theafliberceptarm, P = 0.02 in thebevacizumabarm; ΔVALS > 10 versus < 5; P < 0.001 for both aflibercept and bevacizumab). When month 3 measures are considered jointly, ΔVALS effect remains significant for average ΔVALS from months 4 to 12 (aflibercept: P = 0.002; bevacizumab: P < 0.0001) but not CPT (aflibercept: P = 0.18; bevacizumab: P = 0.22). While both month 3 ΔVALS and CPT are predictive of ΔVALS after month 3 through month 12, early ΔVALS has a stronger relationship than CPT with later ΔVALS. SCORE2 registration number is NCT01969708.

Ophthalmological assessment of crizotinib in advanced non-small-cell lung cancer

ObjectivesDuring crizotinib clinical evaluation, visual disturbances, generally of grade 1 severity, were frequently reported adverse events (AE). Consequently, ophthalmologic assessments were included in a patient subgroup enrolled in PROFILE 1001 (NCT00585195), a phase 1, open-label, single-arm trial of crizotinib in patients with advanced non-small-cell lung cancer and are reported here. Materials and methodsAt least 30 patients were required to undergo ophthalmologic assessments, including: best-corrected visual acuity (BCVA), refractive error, pupil size, slit-lamp anterior segment biomicroscopy, intraocular inflammation, intraocular pressure, retinal fundoscopic exams, fundus photography, ocular characteristics, and optical coherence tomography (OCT). Scheduled assessments included those at baseline, Cycle 1 Day 15, Cycle 3 Day 1 (C3D1), annually during treatment, and end of treatment (28 days after last crizotinib dose). ResultsThirty-three patients completed all required ophthalmologic assessments through C3D1, and 22 (66.7 %) had abnormal findings on ≥1 ophthalmologic test. Clinically important changes were ≥2-line loss in BCVA in 10 patients (30.3 %), >±1.25-diopter change in refractive error in 3 patients (9.1 %), >±2-mm change pupillary diameter change in 3 patients (9.1 %), and >50 μm increase in OCT center point thickness in 7 patients (21.2 %). Three patients (15 %) reported clinically significant abnormalities in anterior segment biomicroscopy (grade 1 cataract [n = 2], grade 1 Visual Impairment [n = 1]). No permanent treatment discontinuations were associated with ophthalmologic findings changes. Twenty-four patients (72.7 %) reported ≥1 ocular all-causality treatment-emergent AE (TEAE); none required dose reduction or permanent discontinuation, but 2 required temporary dosing interruption. Although TEAEs and ophthalmologic findings may not have occurred concurrently, of 24 patients with ≥1 all-causality ocular TEAE, 18/24 (75.0 %) had ≥1 abnormal ophthalmologic finding and 6/24 (25 %) had none; and of 9 patients without an all-causality ocular TEAE, 4/9 (44.4 %) had ≥1 abnormal ophthalmologic finding and 5/9 (55.6 %) had none. Of the 18 patients with ≥1 abnormal ophthalmologic finding, 9 (50 %) had preexisting ocular conditions. ConclusionDuring crizotinib treatment, ophthalmologic changes from baseline did not appear to be associated with patient-reported ocular TEAEs. Abnormal ophthalmologic findings occurred in the context of preexisting conditions for a number of patients. No ophthalmologic changes from baseline or ocular all-causality TEAEs required permanent treatment discontinuation.

Low recurrence of diabetic macular edema, 6 months after focal photocoagulation.

To identify the proportion of eyes with recurrence of diabetic macular edema, six months after focal photocoagulation. Non-experimental, analytical, cross-sectional and prospective study in patients with diabetic macular edema treated with focal photocoagulation. The proportion and 95% confidence intervals (95% CI) of eyes with recurrence of edema were identified; the distribution of anatomical variables and visual acuity was compared between eyes with and without recurrence, using Mann-Whitney's U. 145 eyes were evaluated, and only 10 (95%CI: 2.8-11) had a recurrence. Center point thickness and center field thickness means were higher in eyes with recurrence than in eyes without it, but the difference of change mean betwwen groups was not statistically significant. The proportion of recurrent diabetic macular edema recurrence six months after successful focal photocoagulation was lower than the one reported for other treatments of diabetic macular edema, and by recent studies that used photocoagulation.

IDENTIFICATION OF FACTORS RELATED TO SUBFOVEAL DETACHMENT SECONDARY TO EPIRETINAL MEMBRANE.

To demonstrate factors related to the presence of subfoveal detachment (SD) secondary to epiretinal membrane (ERM) and to characterize the predictors for the resolution of SD after membrane peeling. A retrospective chart review was conducted for the patients who underwent pars plana vitrectomy for the idiopathic ERM peeling. Preoperative spectral domain optical coherence tomography characteristics of the eyes including central foveal thickness, foveal center point thickness, presence of intraretinal cyst, continuity of the membrane, area of the membrane within fovea (1 mm), and entire macula (6 mm) were evaluated to find the best predictors for the presence of SD. These predictors as well as perioperative parameters including use of internal tamponade and volume of SD were considered for time of resolution of SD. Of 158 included eyes, 20.2% eyes (32 eyes) had SD, and the presence of SD was significantly related to involvement of the membrane within the macula. After surgery, SD completely resolved in 90.6% of eyes (29 eyes) at a median of 2.97 months (range: 0.03-12.0 months). The area of the membrane within fovea was the only significant predictor for time to resolution of SD (hazard ratio = 1.20, 95% confidence interval = 1.100-1.324, P = 0.021). A small percent of eyes showed some further changes including fluctuation (6.2%) or persistence (3.1%) of fluid. A larger extension of ERM over the macula is related to higher likelihood of the presence of SD. Time for resolution of subfoveal detachment does not seem to be affected by the preoperative and perioperative factors except the extent of membrane within 1,000 μm of the fovea.

Three-Year Follow-Up of Phase 1 and 2a rAAV.sFLT-1 Subretinal Gene Therapy Trials for Exudative Age-Related Macular Degeneration

To assess the safety and the 3-year results of combined phase 1 and 2a randomized controlled trials of rAAV.sFLT-1 gene therapy (GT) for wet age-related macular degeneration. Phase 1/2a clinical trial. Patients were prospectively randomized into control (n= 13) and GT (n= 24) groups. GT patients received 1X1011vg rAAV.sFLT-1 and were seen every month for 1 year then as needed every 1 to 2months. They were given retreatment anti-vascular endothelial growth factor injections according to predetermined criteria. At 12months, GT patients were divided into 2 groups: HD-1 (n= 14), requiring <2, and HD-2 (n= 10), requiring >2 retreatments. Between 1 year and 3 years there were 3 adverse events (AEs) and 33 serious AEs reported. Of these, 15 occurred in the 13 control subjects and 21 in the 24 GT patients. Except for 1 case of transient choroiditis in a control patient, serious AEs were deemed to be unrelated to the study. Control patients received a median of 7.0 retreatments and lost a median of 7.0 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, HD-1 patients received a median of 2.5 retreatments and lost a median of 4.0 ETDRS letters, and HD-2 patients received a median of 11.0 retreatments and lost a median of 7.0 ETDRS letters over 3 years. Center point thickness fluctuated. Thirty-three percent of control subjects, 44% of HD-2 patients, and 51% of HD-1 patients showed maintenance of baseline visual acuity. Four HD-1 patients (34%) maintained significant visual improvement at 3 years. None of these observations were statistically significant. Given the small number of patients, this study was unable to unequivocally confirm the existence of a biologic efficacy signal; however, it confirmed that rAAV.sFLT-1 gene delivery was well tolerated among the elderly.

Imaging Characteristics of Choroidal Neovascular Lesions in the AREDS2-HOME Study: Report Number 4

To characterize choroidal neovascular (CNV) lesions and the corresponding change in visual acuity (VA) in eyes that converted to neovascular age-related macular degeneration (AMD) in the Age-Related Eye Disease Study 2-HOme Monitoring of the Eye Study. (AREDS2-HOME Study). Cohort study. A total of 1520 participants at risk of developing CNV were enrolled, each of whom contributed 1 or both study eye(s) that had a best-corrected VA letter score of ≥54 letters (Snellen equivalent 20/60) and ≥1 large (≥125 μm) macular druse in the absence of neovascular AMD or central geographic atrophy. A multicenter clinical trial comparing standard care (SC) versus SC plus ForeseeHome (FH; Notal Vision, Manassas, VA) monitoring strategy in the detection of neovascular AMD. Fluorescein angiograms (FA) and OCT were evaluated by an independent reading center (RC) from the visit in which the ophthalmologist identified progression to CNV (n= 82 eyes). Development of CNV on OCT, FA, or both. The RC confirmed CNV in 67 of 82 eyes (82%); lesions were confirmed in 42 of 70 eyes (60%) with FA, 59 of 72 eyes (82%) with OCT, and on both images in 34 of 67 eyes (51%). Among the FA-confirmed cases, the median lesion size was 0.82 disc area (DA); lesions were subfoveal in 40.5%, occult CNV composition was present in 54.8%, and associated hemorrhage in 50%. Median (interquartile range [IQR]) lesion size on FA was 0.23 (0.0-0.91) DA versus 0.70 (0.0-1.50) DA, P= 0.051) in the FH and SC eyes, respectively. Among the OCT-confirmed cases median (IQR) center point thickness was 209 (175-274) μm, retinal pigment epithelial lesion complex was present in 86.4%, and subretinal fluid (SRF) was present in 76.3%. The median change in VA from baseline was -4.0 letters and -10.0 letters in the FH and SC eyes (P= 0.008) confirmed as CNV at the RC. Incident CNV lesions were more prevalent on OCT images than on FA; however, the use of both OCT and FA enhanced detection of incident lesions. Lesions were smaller and associated with less vision loss among eyes in the FH group.

OUTER RETINAL LAYER THICKNESS AS GOOD VISUAL PREDICTOR IN PATIENTS WITH DIABETIC MACULAR EDEMA.

To evaluate the relationship between outer retinal layer (ORL) thickness in diabetic macular edema to visual acuity (VA). Ninety-five eyes were included in this prospective nonrandomized case-control study. They divided into 30 cases of healthy normal subjects and 65 cases of nonproliferative diabetic retinopathy with diabetic macular edema. Complete ophthalmic examination and spectral domain-optical coherence tomography were done for all cases and analyzed to measure central foveal point thickness (CFT), ORL thickness at fovea, and subfoveal choroidal thickness. The ORL thickness was significantly thinner in diabetic macular edema group (85.3 μm) than controls (99.9 μm) (P = 0.002). There was higher significant correlation between ORL thickness and logMAR VA (r = -0.87, P < 0.001) than correlation between CFT and VA (r = 0.18, P = 0.16). The cutoff point of the relationship between ORL thickness and VA was 88 μm with moderate sensitivity (81%) and high specificity (88%), below which vision is affected. Outer retinal layer thickness is significantly related to subfoveal choroidal thickness but not CFT. This study revealed reduction in ORL thickness in diabetic macular edema. There is a higher and stronger correlation between ORL thickness and vision than that between CFT and vision.