Optical Coherence Tomography Central Subfield Thickness Research Articles

Use of Adjunctive Corticosteroid With Antivascular Endothelial Growth Factor Agents in the Treatment of Choroidal Neovascular Membrane Associated With Presumed Ocular Histoplasmosis

Purpose: To evaluate the impact of combination treatment of antivascular endothelial growth factor (anti-VEGF) intravitreal injections and corticosteroids in patients with choroidal neovascularization (CNV) secondary to presumed ocular histoplasmosis syndrome (POHS). Methods: A retrospective multicenter study was conducted in a cohort from Illinois and Missouri. Patients were identified over an 8-year period, and data were evaluated over a 1-year study window commencing with treatment initiation. Group 1 included patients treated with intravitreal injections of anti-VEGF, and group 2 included those who received intravitreal injections of anti-VEGF and adjuvant corticosteroids. Optical coherence tomography (OCT) measurements and increases in Early Treatment Diabetic Retinopathy Study (ETDRS) letter score were compared between each group. Results: Using the method of last visit carried forward, the visual acuity (VA) in group 2 was 6.42 ETDRS letters better than the VA in group 1 at the final assessment. Patients in group 2 had a mean ETDRS letter gain of 21.50 ( P = .06) from the initial baseline vision. The average amount of decrease in OCT central subfield thickness compared with baseline was lower in group 1 (80.9 ± 129.8 µm) vs group 2 (102.8 ± 90.40 µm) at the 1-year follow-up visit ( P = .25). Conclusions: Approved treatment of CNV secondary to POHS is limited. Adjuvant corticosteroid treatment in patients with CNV secondary to POHS may provide better long-term vision and OCT outcomes than anti-VEGF alone and may offer an additional therapy option for these patients.

Association between Retinal Thickness Variability and Visual Acuity Outcome during Maintenance Therapy Using Intravitreal Anti-Vascular Endothelial Growth Factor Agents for Neovascular Age-Related Macular Degeneration.

Previous studies based on clinical trial data have demonstrated that greater fluctuations in retinal thickness during the course of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD) is associated with poorer visual acuity outcomes. However, it was unclear whether similar findings would be observed in real-world clinical settings. This study aimed to evaluate the association between retinal thickness variability and visual outcomes in eyes receiving anti-VEGF therapy for nAMD using pro re nata treatment regimen. A total of 64 eyes which received intravitreal anti-VEGF therapy (bevacizumab, ranibizumab or aflibercept) for the treatment of nAMD were evaluated. Variability in spectral-domain optical coherence tomography (OCT) central subfield thickness (CST) was calculated from the standard deviation (SD) values of all follow-up visits after three loading doses from month 3 to month 24. Eyes were divided into quartiles based on the OCT CST variability values and the mean best-corrected visual acuity values at 2 years were compared. At baseline, the mean ± SD logMAR visual acuity and CST were 0.59 ± 0.39 and 364 ± 113 µm, respectively. A significant correlation was found between CST variability and visual acuity at 2 years (Spearman’s ρ = 0.54, p < 0.0001), indicating that eyes with lower CST variability had better visual acuity at 2 years. Eyes with the least CST variability were associated with the highest mean visual acuity improvement at 2 years (quartile 1: +9.7 letters, quartile 2: +1.1 letters, quartile 3: −2.5 letters, quartile 4: −9.5 letters; p = 0.018). No significant difference in the number of anti-VEGF injections was found between the four CST variability quartile groups (p = 0.21). These findings showed that eyes undergoing anti-VEGF therapy for nAMD with more stable OCT CST variability during the follow-up period were associated with better visual outcomes. Clinicians should consider adopting treatment strategies to reduce CST variability during the treatment course for nAMD.

Association Between Change in Visual Acuity and Change in Central Subfield Thickness During Treatment of Diabetic Macular Edema in Participants Randomized to Aflibercept, Bevacizumab, or Ranibizumab

The determination of optical coherence tomography (OCT) central subfield thickness (CST) is an objective measure, and visual acuity (VA) is a subjective measure. Therefore, using OCT CST changes as a surrogate for VA changes in diabetic macular edema seems reasonable. However, studies suggest that change in OCT CST following anti-vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema is correlated with changes in VA but varies substantially among individuals, and so may not be a good surrogate for changes in VA. To determine associations between changes in VA and changes in OCT CST across 3 anti-VEGF agents (aflibercept, bevacizumab, or ranibizumab) used in a randomized clinical trial for diabetic macular edema. Post hoc analyses were conducted of DRCR Retina Network Protocol T among 652 of 660 participants (98.8%) meeting inclusion criteria for this investigation. The study was conducted between August 22, 2012, and September 23, 2015. The post hoc data collection and analysis were performed from May 29 to July 11, 2018. Six monthly intravitreous anti-VEGF injections (unless success was achieved after 3-5 months) were administered; subsequent injections or focal/grid laser photocoagulation treatments were given as needed per protocol to achieve stability. Association between changes in VA letter score with changes in CST at 12, 52, and 104 weeks after randomization to aflibercept, bevacizumab, or ranibizumab. Of the 652 participants, 304 were women (46.6%); median age was 61 years (interquartile range, 54-67 years). The correlation between CST and VA at the follow-up visits was 0.24 (95% CI, 0.16-0.31) in 616 patients at 12 weeks, 0.31 (95% CI, 0.24-0.38) in 609 patients at 52 weeks, and 0.23 (95% CI, 0.15-0.31) in 566 patients at 104 weeks. The correlation coefficients of change in VA vs change in OCT CST for these time intervals were 0.36 (95% CI, 0.29-0.43) at 12 weeks, 0.36 (95% CI, 0.29-0.43) at 52 weeks, and 0.33 (95% CI, 0.26-0.41) at 104 weeks. Changes in CST appear to account for only a small proportion of the total variation in changes in VA. These findings do not support using changes in OCT CST as a surrogate for changes in VA in phase 3 clinical trials evaluating anti-VEGF for diabetic macular edema or as a guide to inform the physician or patient about changes in VA after anti-VEGF treatment. ClinicalTrials.gov identifier: NCT01627249.

Optical coherence tomography angiographic, visual acuity and anatomic outcomes with aflibercept for diabetic macular edema after bevacizumab and/or ranibizumab.

Background/objectives: To evaluate the safety and efficacy of aflibercept in eyes with persistent diabetic macular edema (DME) after treatment with bevacizumab and/or ranibizumab. Subjects/methods: Open-label, prospective study of intravitreal aflibercept injection in eyes with persistent DME after chronic, recent, and frequent bevacizumab and/or ranibizumab. Results: Thirty eyes were enrolled. Mean change in best corrected visual acuity (BCVA) from baseline to 52 weeks was +7 letters. The mean change in optical coherence tomography (OCT) central subfield thickness (CST) from baseline to 52 weeks was -118 um. At week 52, 70% of eyes with a baseline CST>350 um demonstrated>15% reduction in OCT CST. Forty-eight percent of eyes demonstrated no OCT evidence for DME at last visit. OCT-angiography demonstrated vascular density improvement in the deep capillary plexus. No significant ocular adverse events were observed. Conclusion: Aflibercept demonstrated beneficial visual and anatomic outcomes in patients with persistent DME following bevacizumab and/or ranibizumab.

Endolaserless Vitrectomy With Intravitreal Aflibercept Injection for Proliferative Diabetic Retinopathy-Related Vitreous Hemorrhage (LASER LESS TRIAL)

Purpose: For proliferative diabetic retinopathy (PDR) eyes not requiring vitrectomy, Diabetic Retinopathy Clinical Research Protocol S and the CLARITY trial demonstrated better visual function and anatomical outcomes with less proliferative and diabetic macular edema consequences in the antivascular endothelial growth factor groups compared to the panretinal photocoagulation groups. Intravitreal aflibercept injection (IAI) may represent a useful therapy with vitrectomy for PDR-related vitreous hemorrhage (VH) as a viable alternative to intraoperative endolaser during vitrectomy. We will determine the safety and efficacy when aflibercept is used for PDR-related VH with endolaserless vitrectomy. Methods: Evaluation of endolaserless vitrectomy and 2 mg IAI for PDR-related VH. Eyes receive 1 preoperative and intraoperative IAI followed by randomization to a q8week group receiving 4 postoperative q4week IAI followed by q8week IAI or q16week group receiving 2 postoperative q4week IAI followed by q16week IAI. Main Outcome Measures: Herein, we present pooled safety and efficacy outcomes through 4 months. Results: Twenty-one of 24 eyes were randomized. Preoperative average visual acuity (VA) was 36 letters (20/200). At 4-month follow-up, 18 of 21 randomized eyes showed an average VA of 72 letters (20/40) with an average visual gain of 38 (range, 0-84 gain) letters. Average optical coherence tomography (OCT) central subfield thickness (CST) at 1-month postoperative follow-up was 311 µm. Average OCT CST at 4-month follow-up was 272 µm (average thinning of 38 µm). No significant short-term ocular or systemic adverse events were observed through 4 months. Conclusions: Endolaserless vitrectomy with IAI for PDR-related VH demonstrates short-term safety with significant VA improvement.

Diabetic Retinopathy Phenotypes of Progression to Macular Edema: Pooled Analysis From Independent Longitudinal Studies of up to 2 Years' Duration.

To test the risk of progression to macular edema (ME) of different phenotypes of mild nonproliferative diabetic retinopathy (NPDR). Data from 882 patients with mild NPDR, Early Treatment Diabetic Retinopathy Study grades 20 and 35, with no prior laser treatment, enrolled in four separate longitudinal studies during 2007-2015 using the same reading center and with the same inclusion criteria and were pooled for analysis. One eye per patient was followed for up to 2 years until development of ME. Ophthalmological examinations included best corrected visual acuity, color fundus photography (CFP), and optical coherence tomography (OCT). They were performed at baseline and 6 months, with the last visit at 12 or 24 months, depending on the study. The eyes/patients were classified as belonging to phenotypes A, B, and C on the basis of OCT central subfield thickness and microaneurysm activity. A total of 882 eyes/patients performed the 12- or 24-month visit or developed ME. Of these 882 eyes/patients that completed the studies, 103 developed ME, 14 from phenotype A (14 of 466: 3.0%), 48 from phenotype B (48 of 164: 18.6%), and 41 from phenotype C (41 of 252: 16.3%). Eyes/patients from phenotypes B and C showed much higher risks for ME development compared with phenotype A: odds ratio (OR) 95% confidence interval (CI): 13.30 (7.09-24.97) P < 0.001; OR (CI): 6.32 (3.36-11.90) P < 0.001, respectively. NPDR phenotypes based on microaneurysm turnover and central macular thickness OCT at the 6-month visit using CFP and OCT, both noninvasive examinations, identified the eyes at increased risk of developing ME.

HYPERREFLECTIVE INTRARETINAL SPOTS IN RADIATION MACULAR EDEMA ON SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

To better pathophysiologically characterize macular edema secondary to eye irradiation, analyzing the presence of optical coherence tomography (OCT) hyperreflective spots. Twenty-five consecutive eyes affected by radiation maculopathy, secondary to irradiation for a primary uveal melanoma, without macular involvement in the irradiation field, were consecutively enrolled. All subjects underwent full ophthalmologic examination, including fluorescein angiography, color fundus photography, and spectral domain OCT, even in en face modality. Optical coherence tomography central subfield thickness was stratified into the following 3 categories: <400 μm, 400 to 600 μm, and >600 μm. Spectral domain OCT images were analyzed to measure and localize hyperreflective spots by two independent masked graders. Hyperreflective spots were documented in all eyes (100%). Hyperreflective spots significantly increased in number according to OCT central subfield thickness (<400 μm, 400-600 μm, >600 μm, P < 0.05). The intergrader agreement was at least substantial for all measurements (intraclass correlation coefficient: 0.80). Spectral domain OCT documents discrete intraretinal reflectivity changes (hyperreflective spots) in all (studied) eyes affected by radiation maculopathy. Hyperreflective spots increase in number with increasing central subfield thickness and could be considered as a new clinical biomarker of intraretinal inflammation in patients affected by macular edema secondary to irradiation for uveal melanoma.

Fellow eye effect of unilateral intravitreal bevacizumab injection in eyes with diabetic macular edema

Anti-vascular endothelial growth factor compounds are routinely used for the treatment of diabetic macular edema (DME). We aim to evaluate for the existence and magnitude of treatment effect on fellow un-injected eyes. A consecutive group of patients with bilateral DME who received unilateral bevacizumab injections was retrospectively evaluated. Data collected included demographics, ophthalmic and systemic findings, and optical coherence tomography (OCT) measurements of macular thickness. Thirty-five patients were evaluated. Mean follow-up was 245 days (range: 30-800), and the mean number of bevacizumab injections was 3.6 (range: 1-11). At end of follow-up, the mean (SD) OCT central subfield thickness reduced by 72 ± 112 micron in the injected eye (from 469 ± 139 to 397 ± 120 micron; P=0.001), while in the non-injected eye it reduced by 49 ± 75 micron (from 380 ± 130 to 331 ± 106 micron; P<0.001). Sixteen injected eyes (45.7%) showed central subfield thickness reduction of ≥50 micron while 10 (28.6%) non-injected eyes showed such thickness reduction. Improved VA following treatment was detected in 14 (40%) injected eyes and in 15 (43%) non-injected eyes. Unilateral bevacizumab injections in patients with bilateral DME are often associated with bilateral response. Anti-vascular endothelial growth factor compounds are routinely used for the treatment of diabetic macular edema (DME). In this retrospective study, we show that unilateral bevacizumab injections often result in reduction of the macular thickness in the fellow un-injected eye.

Sustained-Release Intravitreal Liquid Drug Delivery Using Triamcinolone Acetonide for Cystoid Macular Edema in Retinal Vein Occlusion

To investigate side effects seen with this formulation and to search for evidence of effectiveness after a single intravitreal injection of IBI-20089 in eyes with cystoid macular edema (CME) secondary to retinal vein occlusion. Prospective, phase 1 clinical trial. Ten patients with chronic CME resulting from retinal vein occlusion. Patients received a single intravitreal injection of IBI-20089 using a sequential dose escalation schedule. Each cohort consisted of 5 patients who received the intravitreal injection of the sustained liquid drug delivery system containing either 6.9 mg (25 μl) triamcinolone acetonide (TA; cohort 1) or 13.8 mg (50 μl) TA (cohort 2). At each study visit, best-corrected visual acuity testing, slit-lamp biomicroscopy, IOP measurement, dilated ophthalmoscopy, fundus photography and optical coherence tomography (OCT) were performed. Patients also underwent laboratory testing and physical examinations to monitor for any systemic adverse events. Optical coherence tomography central subfield thickness, ocular and systemic adverse events. In cohort 1, mean baseline OCT central subfield thickness (CST) was 477 μm and decreased to 369 μm at day 1 (P<0.06), 387 μm at day 30 (P = 0.18), and 251 μm at day 360 (P = 0.46). In cohort 2, mean baseline OCT CST was 518 μm and decreased to 404 μm at day 1 (P = 0.134), 289 μm at day 30 (P = 0.003), 207 μm at day180 (P = 0.004), and 278 μm at day 360 (P = 0.009). Related adverse events included elevation of IOP in 3 patients, in 2 because of neovascular glaucoma (not related to study drug) and in 1 who required a glaucoma tube shunt. A single intravitreal injection of IBI-20089 resulted in a controlled and sustained delivery of a TA. Side effects included elevated IOP in 3 eyes, 2 of which had neovascular glaucoma.

Vitrectomy Outcomes in Eyes with Diabetic Macular Edema and Vitreomacular Traction

To evaluate vitrectomy for diabetic macular edema (DME) in eyes with at least moderate vision loss and vitreomacular traction. Prospective cohort study. The primary cohort included 87 eyes with DME and vitreomacular traction based on investigator's evaluation, visual acuity 20/63-20/400, optical coherence tomography (OCT) central subfield >300 microns and no concomitant cataract extraction at the time of vitrectomy. Surgery was performed according to the investigator's usual routine. Follow-up visits were performed after 3 months, 6 months (primary end point), and 1 year. Visual acuity, OCT retinal thickening, and operative complications. At baseline, median visual acuity in the 87 eyes was 20/100 and median OCT thickness was 491 microns. During vitrectomy, additional procedures included epiretinal membrane peeling in 61%, internal limiting membrane peeling in 54%, panretinal photocoagulation in 40%, and injection of corticosteroids at the close of the procedure in 64%. At 6 months, median OCT central subfield thickness decreased by 160 microns, with 43% having central subfield thickness <250 microns and 68% having at least a 50% reduction in thickening. Visual acuity improved by > or =10 letters in 38% (95% confidence interval, 28%-49%) and deteriorated by > or =10 letters in 22% (95% confidence interval, 13%-31%). Postoperative complications through 6 months included vitreous hemorrhage (5 eyes), elevated intraocular pressure requiring treatment (7 eyes), retinal detachment (3 eyes), and endophthalmitis (1 eye). Few changes in results were noted between 6 months and 1 year. After vitrectomy performed for DME and vitreomacular traction, retinal thickening was reduced in most eyes. Between 28% and 49% of eyes with characteristics similar to those included in this study are likely to have improvement of visual acuity, whereas between 13% and 31% are likely to have worsening. The operative complication rate is low and similar to what has been reported for this procedure. These data provide estimates of surgical outcomes and serve as a reference for future studies that might consider vitrectomy for DME in eyes with at least moderate vision loss and vitreomacular traction.

Randomized Trial of Peribulbar Triamcinolone Acetonide with and without Focal Photocoagulation for Mild Diabetic Macular Edema: A Pilot Study

To provide pilot data on the safety and efficacy of anterior and posterior sub-Tenon injections of triamcinolone either alone or in combination with focal photocoagulation in the treatment of mild diabetic macular edema (DME). Prospective, phase II, multicenter, randomized clinical trial. One hundred nine patients (129 eyes) with mild DME and visual acuity 20/40 or better. The participants were assigned randomly to receive either focal photocoagulation (n = 38), a 20-mg anterior sub-Tenon injection of triamcinolone (n = 23), a 20-mg anterior sub-Tenon injection followed by focal photocoagulation after 4 weeks (n = 25), a 40-mg posterior sub-Tenon injection of triamcinolone (n = 21), or a 40-mg posterior sub-Tenon injection followed by focal photocoagulation after 4 weeks (n = 22). Follow-up visits were performed at 4, 8, 17, and 34 weeks. Change in visual acuity and retinal thickness measured with optical coherence tomography (OCT). At baseline, mean visual acuity in the study eyes was 20/25 and mean OCT central subfield thickness was 328 mum. Changes in retinal thickening and in visual acuity were not significantly different among the 5 groups at 34 weeks (P = 0.46 and P = 0.94, respectively). There was a suggestion of a greater proportion of eyes having a central subfield thickness less than 250 mum at 17 weeks when the peribulbar triamcinolone was combined with focal photocoagulation. Elevated intraocular pressure and ptosis were adverse effects attributable to the injections. In cases of DME with good visual acuity, peribulbar triamcinolone, with or without focal photocoagulation, is unlikely to be of substantial benefit. Based on these results, a phase III trial to evaluate the benefit of these treatments for mild DME is not warranted.

Reproducibility of Macular Thickness and Volume Using Zeiss Optical Coherence Tomography in Patients with Diabetic Macular Edema

To evaluate optical coherence tomography (OCT) reproducibility in patients with diabetic macular edema (DME). Prospective 1-day observational study. Two hundred twelve eyes of 107 patients with DME involving the macular center by clinical examination and OCT central subfield thickness of > or =225 microm. Retinal thickness was measured with the OCT3 system, and scans were evaluated by a reading center. Reproducibility of retinal thickness measurements was assessed, and 95% confidence intervals (CIs) for a change in thickness were estimated. Reproducibility of OCT-measured central subfield thickness. Reproducibility was better for central subfield thickness than for center point thickness (half-width of the 95% CI for absolute change, 38 microm vs. 50 microm, and for relative change, 11% vs. 17%, respectively; P<0.001). The median absolute difference between replicate measurements of the central subfield was 7 microm (2%). Half-widths of the 95% CI for a change in central subfield thickness were 22, 23, 33, and 56 microm for scans with central subfield thicknesses of <200, 200 to <250, 250 to <400, and > or =400 microm, respectively. When expressed as percentage differences between 2 measurements, half-widths of the 95% CI for a change in central subfield thickness were 10%, 10%, 10%, and 13% for scans with central subfield thicknesses of <200, 200 to <250, 250 to <400, and > or =400 microm, respectively. We were unable to identify an effect on reproducibility of central subfield measurements with respect to the presence of cystoid abnormalities, subretinal fluid, vitreomacular traction, or reduced visual acuity. Reproducibility was better when both scans had a standard deviation (SD) of the center point of <10.0% (half-width of the 95% CI for change, 33 microm vs. 56 microm; P<0.001). Reproducibility is better for central subfield thickness measurements than for center point measurements, and variability is less with retinal thickness when expressed as a percent change than when expressed as an absolute change. A change in central subfield thickness exceeding 11% is likely to be real. Scans with an SD of the center point of > or =10.0% are less reproducible and should be viewed with caution when assessing the validity of an observed change in retinal thickness in patients with DME.