Wide-field optical coherence tomography imaging in diabetic retinopathy.

PURPOSE: To report the individual retinal layer thicknesses up to mid-equator in patients with diabetic retinopathy (DR) using Spectralis (Heidelberg Engineering, Heidelberg, Germany) wide-field optical coherence tomography (OCT). METHODS: Retinal layers were segmented using a custom designed semi-automated algorithm, where reference points were marked by the examiner to enable software to automatically compute the thickness values of each retinal sublayer at an interval of 1 mm from reference points. The values of individual retinal thicknesses in eyes with varying severity of DR were compared with the values of healthy subjects. Generalized estimating equation was performed to compensate for inclusion of both eyes of patients. RESULTS: A total of 64 patients (119 eyes) with a mean age of 68.97 ± 10.27 years were included. Overall, ganglion cell layer (GCL)/ inner plexiform layer (IPL) complex (-31.67 microns, p < 0.001), outer plexiform layer (-6.78 microns, p = 0.002) and photoreceptor layer (-22.90 microns, p < 0.001) showed significant thinning, while outer nuclear layer thickening ( + 68.19 microns, <0.001) was noted in eyes with DM compared to healthy subjects. Thickness changes were significantly more in the macular segment compared to nasal and temporal segments. GCL/ IPL complex and photoreceptor layers were found to be significantly thin in all grades of DR. CONCLUSION: Retinal thicknesses vary significantly in patients with diabetic retinopathy and understanding patterns of these changes across different segments of the wide field OCT may help better elucidate the natural progression of the disease in terms of retinal anatomy.

Evaluation of retinal inflammatory biomarkers after intravitreal steroid implant and Ranibizumab injection in diabetic macular edema.

PURPOSE: To compare the efficacy of intravitreal (IV) ranibizumab (IVR) injection with IV dexamethasone implant (IVDEX) in treatment naive diabetic macular edema (DME) patients with inflammatory component. MATERIALS AND METHODS: Treatment naive DME eyes with subfoveal neurosensorial detachment (SND) and hyperreflective spots (HRS) were treated either three loading doses of IVR (18 eyes) or one dose of IVDEX (19 eyes). Central macular thickness (CMT), height of SND, the number of HRSs scattered on the individual retinal layers and photoreceptor integrity were assessed using spectral domain- optical coherence tomography scans over 3-months follow-up. RESULTS: The mean change in best-corrected visual acuity (BCVA) was -0.11 ± 0.08 logMAR in IVDEX group and -0.04 ± 0.06 logMAR in IVR group at 1-month (p = 0.011). IVDEX group showed statistically significant more increase in BCVA compared to those receiving IVR injections at 2-months (p = 0.004) and 3-months (p = 0.017) visits. Compared to baseline, the number of total HRSs and the number of HRSs at each individual inner retinal layer significantly decreased in both groups at all follow-up visits. However, IVDEX group showed more decrease in the total number of HRSs at 2- and 3-months (p < 0.001 at 2-months, and p = 0.006 at 3-months) and in the mean number of HRSs located at inner nuclear layer-outer plexiform layer level (p = 0.016 at 1-month, p < 0.001 at 2-months, and p < 0.001 at 3-months). After treatment, the number of HRSs on the outer nuclear layer showed some non-significant increase in both groups. CONCLUSION: HRSs tended to migrate from inner retina to the outer retina in DME eyes by treatment. Dexamethasone seemed to be more effective option in such cases with inflammatory component.

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

PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Imaging in inherited retinal disorders.

Inherited retinal diseases, which results from mutations in over 260 identified genes, affect more than 2 million people globally. The diseases mostly cause severe vision loss in young working population and have severe impact on social economic status of the population. Advances in retinal imaging techniques along with developments in gene identification and cell biology techniques have yielded to a better understanding of the genetic and biochemical mechanisms causing these diseases. Retinal imaging along with through ophthalmological examination is essential to make an accurate diagnosis, to decrease the burden of unneccessary anciliary tests and to select the potential patients that can get benefit from the gene treatment. The purpose of the review is to yield an update on inherited retinal diseases by highlighting microstructural changes in retina and to summarize the retinal changes detected by currently available multimodal imaging techniques.

Influence of vitrectomy on the progression of dry age-related macular degeneration.

PURPOSE: To demonstrate whether pars plana vitrectomy (PPV) changes the progression of dry age-related macular degeneration (AMD) by assessing longitudinal changes in drusen volume over follow-up. METHODS: Dry AMD patients who had undergone unilateral PPV for symptomatic vitreomacular disorders were evaluated for the progression of disease by spectral domain-optical coherence tomography (SD-OCT) features including drusen volume, development of geographic atrophy, or choroidal neovascularization during follow-up. Drusen volume was manually calculated using an image processing software (ImageJ, NIH) on raster SD-OCT scans. Mean change in drusen volume of surgery eyes was compared with values of the fellow eyes of the same subjects (control group). RESULTS: Among 183 eyes with both vitreoretinal disorder and dry AMD, 48 eyes of 24 patients met the inclusion criteria and were included. The mean drusen volume change during a mean of 25.49 ± 23.35 months of follow-up (range: 6.00-86.87 months) was 4.236.899 ± 20.488.913 µm3 in the study eye and 7.796.357 ± 34.798.519 µm3 in the fellow eye (p = 0.297). Best-corrected visual acuity (BCVA) significantly increased from 0.40 ± 0.18 logMAR (≈ 20/50 Snellen equivalent) to 0.32 ± 0.31 (≈ 20/41 Snellen equivalent) after surgery (p = 0.012) in the study group while BCVA remained stable in the control group (0.19 ± 0.34 logMAR [≈ 20/30 Snellen equivalent] at baseline and 0.20 ± 0.31 logMAR [≈ 20/31 Snellen equivalent], p = 0.432). Choroidal neovascularization developed in 1 vitrectomized eye (4.54%) and in 1 eye (4.54%) from the control group during follow-up. CONCLUSION: Vitrectomy did not seem to worsen dry AMD progression; even more visual acuity may improve despite a slight increase in drusen volume following surgery.

Factors associated with extended remission in neovascular age-related macular degeneration on pro re nata treatment protocol.

AIM: To show the characteristics and outcomes of patients with neovascular age-related macular degeneration (nAMD) who had extended remission (ER) while on a pro re nata (PRN) treatment protocol. METHODS: This was a retrospective case-control study of a consecutive series of patients with nAMD treated with a PRN antivascular endothelial growth factor (anti-VEGF) drug regimen. ER was defined as the absence of haemorrhage, intraretinal/subretinal fluid on optical coherence tomography and leakage on fluorescein angiography for 52 weeks after cessation of anti-VEGF therapy. Matching patients with nAMD who did not achieve ER were included as control group. Cox regression analysis was fitted to identify predictors of time to achieve ER and time to recurrence. A logistic regression analysis of baseline characteristics was used to identify predictors of achieving ER. RESULTS: Of 830 eyes treated with anti-VEGF monotherapy, 77 (9.2%) eyes achieved ER during a median follow-up of 236 weeks (range 70-525 weeks). Cox regression analysis showed that ER was achieved earlier in eyes with isolated intraretinal fluid (HR, 2.05; 95% CI 1.929 to 4.520; p=0.045) at presentation. Logistic regression analysis showed that type 3 choroidal neovascularisation (OR, 0.090; 95% CI 0.021 to 0.382; p=0.001), thinner choroid (OR, 0.993; 95% CI 0.988 to 0.998; p=0.004) and absence of macular atrophy (OR, 0.233; 95% CI 0.065 to 0.839; p=0.026) at baseline increased the likelihood of achieving ER. CONCLUSION: ER is achievable in 9.2% of patients under PRN therapy for nAMD. At presentation with nAMD, anatomical features on retinal imaging may predict the likelihood of achieving ER and a shorter time to achieve ER.

Foveal Avascular Zone Distortion in Epiretinal Membrane by Optical Coherence Tomography Angiography.

BACKGROUND AND OBJECTIVE: To show the morphologic changes on the foveal avascular zone (FAZ) in patients with epiretinal membrane (ERM) using optical coherence tomography angiography (OCTA) and to demonstrate the correlation between distortion of FAZ and features of the ERM. PATIENTS AND METHODS: FAZ eccentricity index (longest diameter of FAZ/shortest diameter of FAZ) was measured in 52 patients with ERM and compared with 27 healthy subjects' values. The density of the ERM was quantified using a grading scale (0-3) on multicolor scanning laser images, and spectral-domain OCT characteristics of the eyes were assessed. RESULTS: Of the 52 eyes with ERM, 31 eyes (59.61%) showed some foveal remodeling, including full (13.46%) or partial (30.76%) apparent vascularization of FAZ, presence of a vessel crossing the fovea (9.61%), and horizontal or vertical elongation of FAZ (5.76%). The mean FAZ eccentricity index was 0.84 ± 0.46 (range: 0.0-1.86) in eyes with ERM and 0.98 ± 0.07 (range: 0.96-1.02) in the control subjects, respectively (P = .02). There was a negative significant correlation between FAZ eccentricity index and central macular thickness (P = .04). CONCLUSIONS: Thickening of the central fovea leads to foveal remodeling in ERM eyes, and OCTA enables the visualization of architectural FAZ changes. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:295-301.].

COMPARISON OF RETINAL PATHOLOGY VISUALIZATION IN MULTISPECTRAL SCANNING LASER IMAGING.

PURPOSE: To compare retinal pathology visualization in multispectral scanning laser ophthalmoscope imaging between the Spectralis and Optos devices. METHODS: This retrospective cross-sectional study included 42 eyes from 30 patients with age-related macular degeneration (19 eyes), diabetic retinopathy (10 eyes), and epiretinal membrane (13 eyes). All patients underwent retinal imaging with a color fundus camera (broad-spectrum white light), the Spectralis HRA-2 system (3-color monochromatic lasers), and the Optos P200 system (2-color monochromatic lasers). The Optos image was cropped to a similar size as the Spectralis image. Seven masked graders marked retinal pathologies in each image within a 5 × 5 grid that included the macula. RESULTS: The average area with detected retinal pathology in all eyes was larger in the Spectralis images compared with Optos images (32.4% larger, P < 0.0001), mainly because of better visualization of epiretinal membrane and retinal hemorrhage. The average detection rate of age-related macular degeneration and diabetic retinopathy pathologies was similar across the three modalities, whereas epiretinal membrane detection rate was significantly higher in the Spectralis images. CONCLUSION: Spectralis tricolor multispectral scanning laser ophthalmoscope imaging had higher rate of pathology detection primarily because of better epiretinal membrane and retinal hemorrhage visualization compared with Optos bicolor multispectral scanning laser ophthalmoscope imaging.

AGE-RELATED MACULAR DEGENERATION-ASSOCIATED PERIPAPILLARY CHOROIDAL NEOVASCULARIZATION IN THE ERA OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY.

PURPOSE: To characterize the natural history and response of age-related macular degeneration-associated peripapillary choroidal neovascularization to anti-vascular endothelial growth factor therapy. METHODS: This was a retrospective case series of patients with peripapillary choroidal neovascularization secondary to neovascular age-related macular degeneration. All patients underwent complete ophthalmologic examination and retinal imaging including fluorescein angiography and spectral domain optical coherence tomography at each visit. Eyes with subretinal or intraretinal macular fluid were treated with anti-vascular endothelial growth factor monotherapy using a modified as-needed treatment algorithm. RESULTS: Thirty-three eyes of 27 patients were included. The median age was 82 years (range, 62-94), and the median duration of follow-up was 65 months (range, 6-165). Fourteen eyes (58%) without fovea-involving fluid at baseline subsequently developed exudation after a median observation period of 16 months (range, 4-107). Ten of 24 eyes (42%) without initial macular fluid remained dry during the entire follow-up. The median number of injections required until complete fluid reabsorption was 3 (range, 1-21) during the first treatment cycle. The median time to fluid recurrence was 6 months (range, 3-74). CONCLUSION: Peripapillary choroidal neovascularization secondary to wet age-related macular degeneration has a slow progression, may not require treatment for a prolonged period, and responds rapidly to anti-vascular endothelial growth factor treatment with good visual outcomes.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

ANATOMICAL AND FUNCTIONAL TESTING IN DIABETIC PATIENTS WITHOUT RETINOPATHY: Results of Optical Coherence Tomography Angiography and Visual Acuity Under Varying Contrast and Luminance Conditions.

PURPOSE: To assess early retinal microvascular and functional changes in diabetic patients without clinical evidence of diabetic retinopathy with optical coherence tomography angiography and central visual analyzer. METHODS: This was an observational case-control study of diabetic patients without diabetic retinopathy and nondiabetic controls. Patients underwent optical coherence tomography angiography imaging and visual acuity testing using the central visual analyzer. The foveal avascular zone area and the capillary density in the superficial and deep capillary plexuses were measured manually by a masked grader. RESULTS: Sixty eyes from 35 diabetic patients were included in the study group, and 45 eyes from 31 nondiabetic patients were included in the control group. The foveal avascular zone area was not significantly different between the diabetic group and controls (both P > 0.05). The mean capillary density in the deep capillary plexus was significantly lower in diabetic eyes compared with control eyes (P = 0.04). The mean visual acuity in all central visual analyzer modules was significantly decreased in diabetic patients compared with controls (all P < 0.05). CONCLUSION: Optical coherence tomography angiography was able to detect retinal microvascular changes in the deep capillary plexus, and the central visual analyzer showed signs of decreased visual acuity under conditions simulating suboptimal contrast and glare in diabetic patients without diabetic retinopathy.

Inner retinal thickening in newly diagnosed choroidal neovascularization.

PURPOSE: Automated segmentation of retinal layers by spectral-domain optical coherence tomography (SD-OCT) is usually erroneous in the presence of retinal diseases. The purpose of this study is to report the changes in ganglion cell complex (GCC) comprising retina nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) in neovascular age-related macular degeneration (AMD) patients by manually correcting the automated segmentation errors. METHODS: Thirty eyes of 30 patients with new-onset choroidal neovascularization secondary to neovascular AMD and 30 eyes of 30 healthy subjects were included. The inner retinal thicknesses were measured using early treatment diabetic retinopathy circle in the central 1 mm (fovea) and surrounding 3 mm diameter (parafovea) after checking the accuracy of automated segmentation lines. Manual segmentation was done to ensure the accurate segmentation, when needed. RESULTS: Neovascular AMD patients had thicker mean RNFL, GCL, IPL, and GCC thicknesses within the fovea compared to healthy eyes (p = 0.04, p = 0.001, p = 0.032, and p = 0.005, respectively). In the parafoveal area, among the thickness-related measurements, the only significant difference was a thicker mean RNFL (p = 0.002). CONCLUSION: Diffuse thickening of inner retinal layers in neovascular AMD may overestimate actual GCC thickness within fovea. This pseudo-increase in GCC thickness and inner retinal layers in general likely does not reflect more cells or tissue, but rather diffuse edema which leads to a falsely increased reading of layer thickness. Such false readings may also make the assessment of other conditions that lead to reduced inner retinal layer thickness such as glaucoma, optic nerve disease, or retinovascular occlusions more difficult.

Tear film evaluation by scanning laser ophthalmoscopy during retinal imaging.

PURPOSE:: Herein, we describe a novel finding which appears as a reticular pattern on multicolor confocal scanning laser ophthalmoscopy image during routine imaging of retina and we aim to show whether there is an association between this pattern and dry eye findings. MATERIALS AND METHODS:: A total of 162 eyes of 81 patients that were scheduled for a routine retinal imaging by scanning laser ophthalmoscopy at a vitreoretinal practice underwent dry eye evaluation including corneal and conjunctival lissamine green staining, fluorescein staining, tear break-up time, and tear meniscus height measurement before acquiring any images. Then, multicolor images were taken and graded for the severity of reticular pattern. RESULTS:: Among 150 eyes of 81 patients with gradable multicolor imaging, 45 eyes (30%) had some reticular pattern on multicolor image. Severity of reticular pattern on multicolor imaging was significantly correlated with total lissamine score (rho = 0.378, p = 0.007) and tear meniscus height (rho = -0.408, p = 0.011). Furthermore, they were found to be the best set of predictors for the severity pattern on multicolor imaging (odds ratio = 1.30, 95% confidence interval = 1.01-1.37, p = 0.027 and odds ratio = 0.25, 95% confidence interval = 0.128-0.342, p < 0.001, respectively). CONCLUSION:: Reticular pattern seen on multicolor image while acquiring retinal images using scanning laser ophthalmoscopy may be related to tear film instability. Further modulations of the scanning laser ophthalmoscopy instrument will likely improve this indicator of dry eye syndrome.

Comparison of conventional color fundus photography and multicolor imaging in choroidal or retinal lesions.

PURPOSE: Our purpose was to compare the characteristics of the retinal and choroidal lesions including choroidal nevus, choroidal melanoma and congenital hypertrophy of the retina pigment epithelium using conventional color fundus photography (CFP) and multicolor imaging (MCI). METHODS: The paired images of patients with retinal or choroidal lesions were assessed for the visibility of lesion's border, halo and drusen using a grading scale (0-2). The area of the lesion was measured on both imaging modalities. The same grading was also done on the individual color channels of MCI for a further evaluation. RESULTS: Thirty-three eyes of 33 patients were included. There were no significant differences in the mean border, drusen and halo visibility scores between the two imaging modalities (p = 0.12, p = 0.70, p = 0.35). However, the mean area of the lesion was significantly smaller on MCI than that on CFP (14.9±3.3 versus 18.7±3.4 mm2, p = 0.01). CONCLUSION: The appearance of choroidal and/ or retinal lesions on MCI may be different than that on CFP. Though MCI can provide similar information with CFP for the features of retinal and/ or choroidal lesions including border, halo and drusen; the infrared light reflection on MCI underestimates the extent of the choroidal lesion by 33%.

LONG-TERM REMISSION OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION WITH AS-NEEDED ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY.

PURPOSE: To determine the presenting characteristics of patients with neovascular age-related macular degeneration with long-term remission (LTR), which was defined as the absence of intraretinal/subretinal fluid, or hemorrhage, and absence of leakage on fluorescein angiography for longer than 6 months while on as-needed antivascular endothelial growth factor treatment. METHODS: The presenting characteristics of patients with LTR were compared with a control group including 32 eyes of 28 age-, gender-, and ethnicity-matched patients who did not achieve LTR. RESULTS: Seventy-four percent of patients in the LTR group had Type 1 choroidal neovascular membrane and 18.5% had retinal angiomatous proliferation. In the control group, 28 eyes had Type 1 choroidal neovascular membrane (87.5%), and none of the patients had retinal angiomatous proliferation; overall, there was a significant difference in lesion types between the 2 groups (P = 0.036). Eyes with LTR at presentation had significantly thinner subfoveal choroidal thickness (147 vs. 178 µm, P = 0.04). There was more intraretinal fluid and less subretinal fluid at the presentation in the remission group (59.3% intraretinal fluid and 11.1% subretinal fluid) compared with the control group (28.1% intraretinal fluid and 34.4% subretinal fluid, P = 0.03). CONCLUSION: The presence of retinal angiomatous proliferation, thinner choroidal thickness, more intraretinal fluid, and less subretinal fluid at presentation were associated with LTR in patients receiving as-needed treatment for age-related macular degeneration.

REDUCED GANGLION CELL VOLUME ON OPTICAL COHERENCE TOMOGRAPHY IN PATIENTS WITH GEOGRAPHIC ATROPHY.

PURPOSE: Geographic atrophy (GA) is the sequelae of macular degeneration. Automated inner retinal analysis using optical coherence tomography is flawed because segmentation software is calibrated for normal eyes. The purpose of this study is to determine whether ganglion cell layer (GCL) volume is reduced in GA using manual analysis. METHODS: Nineteen eyes with subfoveal GA and 22 controls were selected for morphometric analyses. Heidelberg scanning laser ophthalmoscope optical coherence tomography images of the optic nerve and macula were obtained, and the Viewing Module was used to manually calibrate retinal layer segmentation. Retinal layer volumes in the central 3-mm and surrounding 6-mm diameter were measured. Linear mixed models were used for statistics. RESULTS: The GCL volume in the central 3 mm of the macula is less (P = 0.003), and the retinal nerve fiber layer volume is more (P = 0.02) in patients with GA when compared with controls. Ganglion cell layer volume positively correlated with outer nuclear layer volume (P = 0.020). CONCLUSION: The patients with geographic atrophy have a small significant loss of the GCL. Ganglion cell death may precede axonal loss, and increased macular retinal nerve fiber layer volumes are not indicative of GCL volume. Residual ganglion cell stimulation by interneurons may enable vision in patients with GA.

Glaucoma after Lens-Sparing Vitrectomy for Advanced Retinopathy of Prematurity.

PURPOSE: To report the incidence of, and factors related to, glaucoma after lens-sparing vitrectomy (LSV) surgery in advanced retinopathy of prematurity (ROP). DESIGN: Retrospective case series at a single tertiary referral pediatric vitreoretinal practice. PARTICIPANTS: Four hundred and one eyes from 270 patients were included. METHODS: The medical records of patients who underwent LSV for stage 4A, 4B, and 5 ROP were retrospectively reviewed. Data were collected from patient charts including gender, gestational age at birth, birthweight, stage of ROP at presentation, prior treatment (laser or cryotherapy), subsequent retinal surgeries, presence of glaucoma, time to glaucoma (interval between LSV and the onset of glaucoma), date of lensectomy (if performed), and retinal attachment status at last visit. Lensectomy was considered as a time-dependent covariate in the analysis. MAIN OUTCOME MEASURES: Incidence of glaucoma and potential risk factors for time to glaucoma. RESULTS: Among 401 eyes with advanced ROP, 40 eyes (10.0%) had glaucoma during a mean of 3.06±4.11 years of follow-up. The incidence of glaucoma was 6.9% (17/247) in stage 4A, 12.0% (16/133) in stage 4B, and 33.3% (7/21) in stage 5 ROP. Twenty-one percent of eyes (87/401) required lensectomy at a mean of 1.23±2.19 years after LSV. In univariate analysis, having stage 5 ROP (vs. stage 4 ROP) and presence of lensectomy were found to be significantly associated with time to glaucoma (hazard ratio = 6.76, 95% confidence interval = 2.19-20.88, P = 0.001; hazard ratio = 3.06, 95% confidence interval = 1.56-6.0, P = 0.001, respectively). In multivariate analysis, lensectomy was the only significant independent factor associated with time to glaucoma (hazard ratio = 2.76, 95% confidence interval = 1.371-5.581, P = 0.004). CONCLUSIONS: Patients with more severe ROP had a higher incidence of glaucoma after lens-sparing vitrectomy. If a patient required lensectomy owing to progression of ROP and/or presence of lens opacity, then the hazard of having glaucoma significantly increased compared with those without lensectomy.

HIGH-DOSE HIGH-FREQUENCY AFLIBERCEPT FOR RECALCITRANT NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To determine the efficacy of monthly (0.1 mL/4 mg) aflibercept for refractory neovascular age-related macular degeneration (wet age-related macular degeneration). METHODS: This was a retrospective interventional case series in which patients with wet age-related macular degeneration were treated with stepwise dose escalation. Nonvitrectomized patients resistant to monthly (Q4W) ranibizumab/bevacizumab were switched to 2 mg aflibercept every 8 weeks. With resistance, they were escalated to Q4W 2 mg aflibercept, then Q4W 4 mg (high dose high frequency, 4Q4W) aflibercept. Resistance was defined as ≥2 recurrences after being dry following ≥3 injections or persistent exudation on treatment of ≥5 injections. RESULTS: Thirty-three eyes of 28 patients were treated with 4Q4W aflibercept and followed for a mean of 16 months. A dry retina (no intraretinal or subretinal fluid) was achieved after initiating 4Q4W aflibercept treatment at a mean of 3.8 months. Central foveal thickness, maximum foveal thickness, intraretinal fluid, subretinal fluid, and retinal pigment detachment height decreased significantly at 1 month after initiating the 4Q4W aflibercept, and the morphologic therapeutic effect was sustained until the last visit. Forty-five percent of eyes had one or more lines of vision improvement. New geographic atrophy developed in 9% of eyes during follow-up. No ocular or systemic adverse events occurred after initiating 4Q4W aflibercept. CONCLUSION: Intravitreal high-dose high-frequency aflibercept is an effective treatment for patients with refractory wet age-related macular degeneration.

QUANTITATIVE ANALYSIS OF THE INNER RETINAL LAYER THICKNESSES IN AGE-RELATED MACULAR DEGENERATION USING CORRECTED OPTICAL COHERENCE TOMOGRAPHY SEGMENTATION.

PURPOSE: To characterize inner retinal damage in patients with dry age-related macular degeneration (AMD) using high-resolution spectral domain optical coherence tomography images. METHODS: Sixty eyes of 60 patients with AMD were categorized using the Age-Related Eye Disease Study (AREDS) severity scale. Spectral domain optical coherence tomography images of these patients were quantified by manually correcting the segmentation of each retinal layer, including the retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer to ensure accurate delineation of layers. The mean ganglion cell complex thickness values (ganglion cell layer + inner plexiform layer + retinal nerve fiber layer) were compared with 30 eyes of 30 healthy subjects. RESULTS: Ninety percent of eyes (81 eyes) required manual correction of segmentation. Compared with healthy subjects, mean ganglion cell complex thicknesses significantly decreased in more advanced dry AMD eyes, and this decrease was predominantly related to a change in inner plexiform layer thickness. There was no significant difference in thickness-related measurements between milder dry AMD (AREDS-2) eyes and healthy eyes (P > 0.05). CONCLUSION: In patients with dry AMD, automatic optical coherence tomography segmentation algorithms may be erroneous. As the severity of dry AMD increases, the inner plexiform layer layer becomes thinned, suggesting that transsynaptic degeneration may be occurring, as the photoreceptor layer is affected by AMD.