The Injection Practice Patterns of Retina Specialists in Managing Exudative Age-Related Macular Degeneration: A Retrospective Study.

Purpose: To compare the PRN anti-VEGF injection patterns of four retina specialists with respect to the visual and anatomic outcomes in the management of wet age-related macular degeneration (AMD). Methods: Medical records of patients who received bevacizumab, ranibizumab, and aflibercept anti-VEGF injections (years 2010-2020) by four retina specialists were reviewed for frequency, injection intervals, best corrected visual acuity (BCVA), and central macular thickness, center involved (CMT) for statistical analysis. Outcomes measured were change in logMAR BCVA and CMT from the first to last injection visit. Results: Out of 137 AMD patients, 172 eyes were injected by four retina specialists in PRN fashion. Although all four specialists started the injection at similar baseline BCVA and CMT (p > 0.1), significant differences in mean injection number (9.0, p = 0.0001), injection intervals (5.06 weeks, p = 0.001), and total length of treatments (53.3 weeks, p = 0.0001) were observed. The mean change in logMAR BCVA between the first and last injection was -0.05, -0.22, 0.07, and 0.06 for the four specialists, respectively (p = 0.031), and the mean change in CMT was -53.3, -41.4, -72.7, and -21.9 µm (p = 0.41), respectively. Conclusion: Despite similar baseline criteria for injections by the retina specialists, different anti-VEGF injection regimens were practiced resulting in variations in BCVA and CMT outcomes. This suggests a need in establishing a universally adoptable injection regimen with possible integration of the confounding factors to reduce burden on both patients and retina specialists.

Subfoveal choroidal thickness following pars plana vitrectomy in tractional diabetic macular edema.

PURPOSE: To evaluate changes in subfoveal choroidal thickness (SCT) in cases of tractional diabetic macular edema (DME) after pars plana vitrectomy (PPV). METHODS: This prospective study included 31 eyes of 31 patients who underwent PPV for the management of tractional DME. Best-corrected visual acuity (BCVA), SCT, and central macular thickness (CMT) were measured before the operation, as well as one, three, and six months following the surgery in the operated eyes and at baseline, as well as six months in the fellow eyes. RESULTS: The SCT decline in eyes with tractional DME was statistically significant six months postoperatively (P = 0.009). A statistically significant decline was observed in the CMT values one, three, and six months postoperatively in eyes with tractional DME (P = 0.02, P < 0.001, and P < 0.001, respectively). There was a statistically significant improvement in the visual acuity of the affected eyes three (P = 0.047) and six months (P = 0.017) postoperatively. CONCLUSION: After PPV for the treatment of tractional DME, a statistically significant decrease in the CMT values is detectable from the first month after surgery, followed by the improvement of BCVA from the third month. It is worth mentioning that a decrease was found in the SCT six months postoperatively.

PRN Treatment of Neovascular AMD with Cycles of Three Monthly Injections.

PURPOSE: To report the one and two year outcome of cycles of three, monthly anti-VEGF injections given upon reactivation of the disease in eyes with neovascular age-related macular degeneration (nAMD). METHODS: Retrospective study of naïve nAMD cases with more than one year of follow-up, treated with a protocol of cycles of three monthly injections of anti-VEGF drugs upon reactivation. Visual acuity (VA) and central macular thickness (CMT) are the main outcome measures. RESULTS: Twenty-six patients with a mean age of 78.15 ± 9.29 years (57.7% female) were included. The mean follow-up was 30.89 ± 6.95 months. Treatment started with bevacizumab in all patients but in six patients was switched to aflibercept due to inadequate response to intravitreal bevacizumab injection. The mean VA at baseline and at 12 and 24 months was 53.87 ± 21.84, 60.54 ± 21.13, and 53.68 ± 27.16 ETDRS letters, respectively. Patients gained a mean of 6.67 ± 13.7 (p = 0.013, 95% CI= 0.60 to 12.65) and 0.77 ± 15.21 (p = 0.4, 95% CI: -5.65 to 7.2) letters at 12 and 24 months. CMT at baseline, 12, and 24 months was 403.55 ± 147.59, 323.95 ± 79.58, and 298.59 ± 77.161 µm, respectively. The number of injections in the first and second years were 7.65 ± 2.64 and 5.52 ± 3.01, respectively. Three eyes (12.5%) lost > 15 letters at 24 months. CONCLUSION: This protocol can stabilize or improve vision in 87.5% of nAMD patients and can reduce the number of visits.

Subretinal leakage of a retinal capillary macroaneurysm - a case report.

BACKGROUND: Report a rare case of retinal capillary macroaneurysm with associated subretinal fluid. CASE PRESENTATION: A 71-year-old male underwent full ophthalmic examination including Optical Coherence Tomography (OCT), Fluorescein Angiography (FA). Fundus examination showed moderate non-proliferative diabetic retinopathy of both eyes with scattered microaneurysms. On initial visit, FA displayed a hyperfluorescent lesion with leakage on late frames in the left eye. OCT revealed the lesion to be spheroid with a hyperreflective wall and hyporeflective lumen in the inner retina, corresponding to a capillary macroaneurysm. Intraretinal cystic fluid surrounded the lesion. On subsequent visit 7 months later, subretinal fluid in the location of the capillary macroaneurysm was noted on OCT. Vision was maintained at 20/30-2 OD, 20/40 OS throughout. No treatment was necessary. CONCLUSION: Subretinal fluid from the capillary macroaneurysm likely developed from its juxtafoveal location and discontinuity of the external limiting membrane (ELM); a barrier preventing flow of intraretinal fluid to the outer retina.

An Analysis of the Areas Occupied by Vessels in the Ocular Surface of Diabetic Patients: An Application of a Nonparametric Tilted Additive Model.

(1) Background: As diabetes melllitus (DM) can affect the microvasculature, this study evaluates different clinical parameters and the vascular density of ocular surface microvasculature in diabetic patients. (2) Methods: In this cross-sectional study, red-free conjunctival photographs of diabetic individuals aged 30-60 were taken under defined conditions and analyzed using a Radon transform-based algorithm for vascular segmentation. The Areas Occupied by Vessels (AOV) images of different diameters were calculated. To establish the sum of AOV of different sized vessels. We adopt a novel approach to investigate the association between clinical characteristics as the predictors and AOV as the outcome, that is Tilted Additive Model (TAM). We use a tilted nonparametric regression estimator to estimate the nonlinear effect of predictors on the outcome in the additive setting for the first time. (3) Results: The results show Age (p-value = 0.019) and Mean Arterial Pressure (MAP) have a significant linear effect on AOV (p-value = 0.034). We also find a nonlinear association between Body Mass Index (BMI), daily Urinary Protein Excretion (UPE), Hemoglobin A1C, and Blood Urea Nitrogen (BUN) with AOV. (4) Conclusions: As many predictors do not have a linear relationship with the outcome, we conclude that the TAM will help better elucidate the effect of the different predictors. The highest level of AOV can be seen at Hemoglobin A1C of 9% and AOV increases when the daily UPE exceeds 600 mg. These effects need to be considered in future studies of ocular surface vessels of diabetic patients.

Endogenous Endophthalmitis: Recommendation for Empiric Dual Antibacterial and Antifungal Therapy.

Purpose: This work compares clinical presentation and course of bacterial and fungal causes of endogenous endophthalmitis (EE). Methods: A single-institutional study of consecutive patients diagnosed with EE was conducted at the University of Pittsburgh Medical Center between September 2015 and September 2018. Exclusion criteria included history of ocular trauma, intraocular surgery or injection 6 months before presentation, or primary external ocular infection. Data included demographics, medical and ocular history, clinical examination, culture data, therapeutic interventions, final corrected visual acuity (VA), and mortality. Results: Thirty-six eyes of 26 patients were diagnosed with EE during a 3-year period. Median age at diagnosis was 55.5 years (range, 19-86 years). Based on ocular and systemic cultures, 19 patients had bacterial EE and 6 patients had fungal EE; findings from all cultures remained negative in 1 patient. All patients had risk factors for EE. Presenting VA, subjective symptom report, and objective measures of intraocular inflammation were similar between bacterial and fungal causes. Overall, EE presented indolently and was initially misdiagnosed in 19% of cases. Complications including final VA less than 20/200, retinal detachment, enucleation, or death within 6 months of diagnosis were equivalent between bacterial and fungal cases. Conclusions: The presentation of EE is remarkably different from that of exogenous endophthalmitis. Without a high index of suspicion, the indolent presentation of EE may lead to misdiagnosis. No clinical features reliably differentiated bacterial and fungal sources. This highlights the importance of considering empiric therapy for antibacterial and antifungal coverage on initial presentation.

Long-Term Intraocular Pressure Changes after Pars Plana Vitrectomy: An 8-Year Study.

PURPOSE: To investigate the long-term changes of intraocular pressure (IOP) after pars plana vitrectomy (PPV). METHODS: This was a retrospective historical cohort study. Patients with a history of vitrectomy in one eye by a single surgeon were enrolled. IOP of the operated eye was compared to the fellow eye. Previous scleral buckling, IOP rise due to surgical/anatomic complications, silicone oil (SO) emulsification, and contralateral ocular hypertension/glaucoma at recruitment were exclusion criteria. "Significant IOP rise" (>6.0 mmHg) and development of open angle glaucoma (OAG) were the main outcome measures. RESULTS: Two hundred and twenty-five eyes were included. Mean and median follow-up duration were 20.6 and 9.0 months, respectively. Mean baseline IOP and mean final IOP were 13.53 ± 3.75 mmHg and 16.52 ± 6.95 mmHg, respectively (P < 0.001). Forty-three patients developed "significant IOP rise" with no statistically significant relation to the indication of vitrectomy, the postoperative lens status, and number of vitrectomies (P = 0.410, P = 0.900, and P = 0.160, respectively). SO injection raised the probability of IOP rise in the long-term (P = 0.028). OAG occurred in 17 patients (7.5%) with no association to SO tamponade (P = 0.840). "Significant IOP rise" and OAG occurred in 3 and 1 control eyes, respectively, significantly lower than the rates in study eyes (P < 0.001). CONCLUSION: Mean IOP slightly rose in the long-term after PPV. SO tamponade was associated with IOP rise in the long-term but not with the incidence of OAG. Both IOP rise and OAG were more probable after vitrectomy.

Development of focal choroidal excavation in non-neovascular age related macular degeneration with pachy-choroid features.

PURPOSE: To present a documented case of development of focal choroidal excavation (FCE) in non-neovascular age related macular degeneration (AMD). METHODS: An 86-year-old female with pachy-choroid was followed clinically for non-neovascular AMD. Successive optical coherence tomography (OCT) scans were reviewed with tracking software. RESULTS: Over the course of follow-up development of a FCE adjacent to a pachy-vessel along with disappearance of the pachy-vessel was documented in OCT. CONCLUSIONS: This case is a documented development of FCE in an eye with pachy-choroid features. The possible mechanism in this scenario may be thrombosis of pachy-vessels.

Ellipsoid Zone Mapping Parameters In Retinal Venous Occlusive Disease With Associated Macular Edema.

PURPOSE: To evaluate the association of baseline ellipsoid zone (EZ) parameters on optical coherence tomography (OCT) as calculated by a semi-automated computer algorithm with baseline visual acuity in eyes with retinal vein occlusion (RVO). DESIGN: Retrospective consecutive case series. SUBJECTS: Patients affected by RVO presenting from January 2011 to December 2014. METHODS: Baseline demographics, clinical characteristics, and SD-OCT data at presentation were collected. Macular cube scans were exported into a retinal layer analysis software platform and outer retinal parameters were evaluated. Outer retinal/EZ parameters included EZ-retinal pigment epithelium (RPE) volume, central foveal EZ-RPE area, EZ-RPE central subfield thickness (CST), and EZ-RPE central foveal thickness (CFT). In addition, en face EZ mapping features were extracted including percent area with EZ attenuation (i.e., EZ-RPE thickness < 20 µm) and percent area with total EZ loss (i.e., EZ-RPE thickness = 0 µm). MAIN OUTCOME MEASURE: Correlation of EZ parameters and baseline visual acuity (VA). Secondary outcome measures: Correlation of EZ parameters with other clinical characteristics and OCT measures of cube volume, cube average thickness, central subfield thickness. RESULTS: One hundred and twelve eyes were included in this analysis. Mean baseline VA was 56.53 ±17.68 ETDRS letters and was inversely associated with total EZ loss and EZ-RPE attenuation (r= - 0.33 and -0.38 respectively, p<0.001). VA was directly associated with all other EZ parameters (r=0.37 to 0.45, p<0.001). The presence of subretinal fluid was strongly linked to central parameters of central foveal EZ-RPE, EZ-RPE-CST, and EZ-RPE-CFT (Kruskal-Wallis test). Conventional OCT parameters (central subfield retinal thickness, cube volume and cube average thickness) did not have significant correlations with EZ measures (-0.30.05). CONCLUSION: Baseline EZ integrity is closely linked to presenting visual acuity in eyes with RVO and macular edema. EZ mapping provides an additional metric for evaluating RVO impact on retinal anatomy and potential function.

Optical Coherence Tomography Angiography in Eyes with Retinal Vein Occlusion.

Optical coherence angiography (OCTA) is a noninvasive technique that has been introduced in recent years to detect ophthalmological pathology. The growing usage of OCTA to detect retinal abnormalities can be attributed to its advantages over the reference-standard fluorescein angiography (FA), although both of these techniques can be used in association. OCTA's advantages include its dye independency, its ability to produce depth-resolved images of retinal and choroidal vessels that yield images of different vascular layers of the retina, and the better delineation of the foveal avascular zone. OCTA's disadvantages include the lack of normalized patient data, artefactual projection issues, and its inability to detect low-flow lesions or pathologic conditions. Different OCTA platforms use unique algorithms to detect microvasculature, which are implemented in both spectral-domain (SD) and swept-source (SS) OCT machines. Microvascular changes in retinal vein occlusions (RVOs) are visible in both the superficial and deep capillary networks of the retina in OCTA. These visualizations include a decrease in foveal and parafoveal vascular densities, non-perfusion areas, capillary engorgement and telangiectasias, vascular tortuosity, microaneurysms, disruption of the foveal perivascular plexus, and formation of collateral vessels. The restricted field of view and inability to show leakage are important limitations associated with the use of OCTA in RVO cases. In this article, we present a brief overview of OCTA and a review of the changes detectable in different slabs by OCTA in RVO cases published in PubMed and Embase.

Switching Anti-Vascular Endothelial Growth Factors in Refractory Neovascular Age-Related Macular Degeneration.

BACKGROUND AND OBJECTIVE: Anti-vascular endothelial growth factor (VEGF) therapy is the treatment of choice for cases with neovascular age-related macular degeneration (AMD). Switching to an alternate anti-VEGF has been suggested as a possible option for resistant cases. The purpose of this review is to evaluate whether the timing of switching affects treatment outcomes. PATIENTS AND METHODS: A review of published literature was performed looking at all studies where patients with refractory neovascular AMD were switched to an alternative anti-VEGF. Studies were then stratified based on the timing of switching into early (< 12 previous injections) and late (> 12 previous injections). RESULTS: A total of 38 studies were identified: 18 where patients were switched early and 20 where they were switched late. Both subgroups showed anatomic improvement after switching, with limited visual gains. CONCLUSION: There are insufficient data to recommend early versus late switching. However, both groups showed a reduction of fluid on optical coherence tomography and visual gains in 25% to 30% of patients. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:166-170.].

Vitreous changes after intravitreal bevacizumab monotherapy for retinopathy of prematurity: a case series.

PURPOSE: Reporting a special clinical finding after intravitreal bevacizumab monotherapy for retinopathy of prematurity. METHODS: In a retrospective case series, the clinical courses of five premature infants with similar vitreous changes after a single dose of intravitreal bevacizumab (IVB) injection without additional laser therapy were reported. RESULTS: The mean post-conceptional age at IVB injection was 39.8 ± 2.2 (range 37-43) weeks. Localized vitreous syneresis and linear fibrotic vitreous condensation occurred 8.2 ± 2.3 weeks after IVB monotherapy in our patients (15.5% of injections). The mean last post injection visit was 61.6 ± 5.3 weeks (post-conceptional age). Further regression and complete retinal vascularization occurred in all patients. CONCLUSIONS: Thread-like vitreous condensation with localized vitreous liquefaction may be related to involutional ROP disease itself, combined to anti VEGF therapy and may be a predictor factor for further regression and retinal vascularization. The case series describes a successful response to anti-VEGF monotherapy with no further complications.

Distribution of Different Sized Ocular Surface Vessels in Diabetics and Normal Individuals.

PURPOSE: To compare the distribution of different sized vessels using digital photographs of the ocular surface of diabetic and normal individuals. METHODS: In this cross-sectional study, red-free conjunctival photographs of diabetic and normal individuals, aged 30-60 years, were taken under defined conditions and analyzed using a Radon transform-based algorithm for vascular segmentation. The image areas occupied by vessels (AOV) of different diameters were calculated. The main outcome measure was the distribution curve of mean AOV of different sized vessels. Secondary outcome measures included total AOV and standard deviation (SD) of AOV of different sized vessels. RESULTS: Two hundred and sixty-eight diabetic patients and 297 normal (control) individuals were included, differing in age (45.50 ± 5.19 vs. 40.38 ± 6.19 years, P < 0.001), systolic (126.37 ± 20.25 vs. 119.21 ± 15.81 mmHg, P < 0.001) and diastolic (78.14 ± 14.21 vs. 67.54 ± 11.46 mmHg, P < 0.001) blood pressures. The distribution curves of mean AOV differed between patients and controls (smaller AOV for larger vessels in patients; P < 0.001) as well as between patients without retinopathy and those with non-proliferative diabetic retinopathy (NPDR); with larger AOV for smaller vessels in NPDR (P < 0.001). Controlling for the effect of confounders, patients had a smaller total AOV, larger total SD of AOV, and a more skewed distribution curve of vessels compared to controls. CONCLUSION: Presence of diabetes mellitus is associated with contraction of larger vessels in the conjunctiva. Smaller vessels dilate with diabetic retinopathy. These findings may be useful in the photographic screening of diabetes mellitus and retinopathy.

Switching Anti-VEGF Drugs in the Treatment of Diabetic Macular Edema.

Since their introduction in the late 2000s, anti-vascular endothelial growth factor (VEGF) agents have become the first-line choice for center-involved diabetic macular edema (DME). Even with its proven effectiveness, there are still cases that do not respond satisfactorily. In those cases, a treatment option is to change to another anti-VEGF drug. In this paper, the authors review studies on switching between different anti-VEGF drugs in the treatment of persistent DME. An extensive bibliographic review was done using PubMed, Embase, and Scopus. Fourteen studies published from March 2010 to April 2017 reporting switching from anti-VEGF drugs in DME treatment were included. All reported good anatomical results after conversion; however, visual acuity outcomes showed great variability between publications. Therefore, switching to other anti-VEGFs in patients with DME not responding to previous anti-VEGF therapy may be an option, but the results are still not well-known due to a lack of randomized clinical trials. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:748-754.].

Utility of 1% Tropicamide in Improving the Quality of Images for Tele-Screening of Diabetic Retinopathy in Patients with Dark Irides.

PURPOSE: To compare the quality of fundus photographs taken before and after instillation of one drop of tropicamide. METHODS: The 45º fundus photographs were taken with a non-mydriatic fundus camera in three conditions of the pupil; pre-mydriatic, 10 minutes after one drop of tropicamide, and fully dilated. Two photographs were taken in each condition; one centered on the macula and the other on the optic disc. Two vitreoretinal specialists graded the images. RESULTS: A total of 1768 fundus photographs of 149 diabetic patients with dark irides were included. There were more ungradable images (38.1% and 50.3%, graders 1 and 2, respectively) in the non-mydriatic state than partially- (4.6% and 11.5%) or fully-dilated (15.4% and 10.0%) conditions (p < 0.001, both graders). Partially and fully dilated states had similar rates of ungradable images (p = 0.56 and p = 0.54, graders 1 and 2, respectively). Test-retest reliability (repeatability) was 92.5% and 74.3% for the two graders, respectively. Inter-grader agreement was moderate (Kappa = 0.50). CONCLUSION: Non-mydriatic fundus photographs have a high rate of ungradable images in patients with dark irides. Instillation of only one drop of tropicamide improves the quality of fundus photographs, which is not furthered by adding more drops. This strategy can be used in tele-ophthalmology programs.

Comparison of four surgical techniques for management of pseudophakic and aphakic retinal detachment: a multicenter clinical trial.

PURPOSE: To compare the visual and anatomical outcomes of four surgical techniques to manage pseudophakic and aphakic retinal detachment (PARD). METHODS: In a multicenter randomized clinical trial, 211 eyes of 211 patients with PARD and proliferative vitreoretinopathy (PVR) grade B or less were randomly assigned to one of the four treatment groups: (1) scleral buckling (SB), 50 eyes, (2) vitrectomy without band, 51 eyes, (3) vitrectomy with encircling band (EB), 58 eyes, and (4) triamcinolone acetonide (TA) assisted vitrectomy, 52 eyes. Patients were followed for 12 months after the surgery. The best-corrected visual acuity (BCVA) and retinal reattachment rate at each follow-up time point were considered as the primary outcome measures. PVR, macular pucker, and cystoid macular edema were considered as the secondary outcomes. RESULTS: Visual improvement was achieved in all treatment groups relative to the baseline at all time points (all Ps < 0.001). There were no statistically significant differences among the groups with regard to BCVA changes. However, there was a significant difference in the slope of visual improvement curve: the SB group had a more rapid visual improvement compared to the vitrectomy with buckle group at month 12 (P = 0.032). The retinal reattachment rates at month 12 were 75, 64.7, 68.5, and 66.7 % in SB, vitrectomy without buckle, vitrectomy with EB, and TA-assisted vitrectomy groups respectively (P > 0.99). There were no statistically significant differences among the groups in terms of adverse events. CONCLUSIONS: SB, TA-assisted vitrectomy, and vitrectomy with and without buckle had comparable outcomes in the management of PARD.