Immunomodulatory Treatment Versus Systemic Steroids in Inflammatory Choroidal Neovascularization Secondary to Idiopathic Multifocal Choroiditis.

PURPOSE: To evaluate the influence of immunomodulatory therapy (IMT) on visual and treatment outcomes of inflammatory choroidal neovascularization (iCNV) in patients affected by multifocal choroiditis (MFC), and to compare them to patients treated with steroids as needed. DESIGN: Multicenter retrospective matched cohort study. METHODS: Patients affected by MFC with iCNV were divided into a IMT group and a "steroids as needed" group and matched according to the time between diagnosis and beginning of systemic treatment. Visual acuity (VA), number of anti-vascular endothelial growth factor (VEGF) intravitreal injections, and number of iCNV reactivations during 2 years of follow-up after treatment initiation were compared between the 2 groups. RESULTS: A total of 66 eyes of 58 patients were included, equally divided into the 2 groups. Patients in the IMT group had a lower relative risk (RR) of iCNV reactivation (0.64, P = .04) and of anti-VEGF intravitreal injection retreatment (0.59, P = .02). Relapses of MFC-related inflammation were independently associated with a higher RRs of iCNV reactivation (1.22, P = .003). Final VA was higher in the IMT compared to the steroids as needed group (mean [SD], 69.1 [15.1] vs 77.1 [8.9] letters, P = .01), and IMT was associated with greater VA gains over time (+2.5 letters per year, P = .04). CONCLUSIONS: IMT was associated with better visual and treatment outcomes in MFC complicated by iCNV compared to steroids as needed. The better outcomes of the IMT group and the association between MFC-related inflammation and iCNV reactivations highlight the need for tighter control of inflammation to prevent iCNV relapses and visual loss.

Lesion area progression in eyes with neovascular age-related macular degeneration treated using a proactive or a reactive regimen.

BACKGROUND: To compare the change in lesion area over 4 years of follow-up in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents using either a proactive or a reactive regimen in routine clinical practice. METHODS: This was a multicentre, retrospective comparative study. Totally, 202 treatment-naïve nAMD eyes (183 patients) received anti-VEGF therapy according to a proactive (n = 105) or reactive (n = 97) regimen. Eyes were included if they had received anti-VEGF injections for a period of at least 4 years and had baseline fluorescein angiography and annual optical coherence tomography (OCT) imaging. Two masked graders independently delineated the lesion's margins from serial OCT images and growth rates were calculated. RESULTS: At baseline, the mean [SD] lesion area was 7.24 [5.6] mm2 in the proactive group and 6.33 [4.8] mm2 in the reactive group respectively (p = 0.22). After four years of treatment, the mean [SD] lesion area in the proactive group was 5.16 [4.5] mm2 showing a significant reduction compared to the baseline (p < 0.001). By contrast, the mean [SD] lesion area kept expanding in the reactive group during the follow-up and was 9.24 [6.0] mm2 at four years (p < 0.001). The lesion area at 4 years was significantly influenced by treatment regimen, baseline lesion area, and proportion of visits with active lesions. CONCLUSIONS: Eyes treated using a reactive strategy had an increased lesion area and worse visual outcomes at 4 years. By contrast, the proactive regimen was associated with fewer recurrences of active disease, shrinkage of the lesion area, and better vision at four years.

Retromode Imaging Technology for Detecting Drusen-Like Deposits in Healthy Adults.

PURPOSE: To investigate the ability of retromode imaging technology to visualize drusen-like deposits (DLDs) in the macular region of healthy individuals without retinal diseases. Additionally, the correlation between subject age and the density of DLDs was assessed and their topographic distribution was evaluated. DESIGN: Prospective, observational, cross-sectional study SUBJECTS: Healthy volunteers (aged ≥ 35 years) without macular diseases. METHODS: This study evaluated macular images in healthy adults using color fundus photography (FP) and retromode imaging. Two masked graders counted the number of DLDs identifiable with each modality. The standardized ETDRS concentric rings were adopted to divide DLDs based on their topographic distribution. MAIN OUTCOME MEASURES: Comparison of the number of DLDs detected with each imaging modality. The association between DLDs and age. The topographic distribution of macular DLDs with retromode imaging. RESULTS: The study included 91 eyes of 52 healthy volunteers (mean ± standard deviation age, 57.9 ± 10.9 years; range, 36-82 years). Overall, at least 1 DLD was present in 63.74% of eyes on color FP and 96.71% on retromode. Retromode imaging allowed detection of significantly more DLDs compared with color FP within the ETDRS grid (median [interquartile range], 4 [1-14] vs. 0 [0-0] respectively; P < 0.001). The density of DLDs was higher in the outer and inner rings compared with the central subfield (relative risk [RR], 16.70; 95% confidence interval [CI], 10.3-27.3 vs. RR 17.1; 95% CI, 10.5-27.6, respectively). Age was significantly correlated with DLDs density in all 3 sectors (all P < 0.05). CONCLUSIONS: Retromode technology allowed the detection of a significantly higher number of DLDs compared with FP in the macula of healthy individuals. This noninvasive imaging modality could be used to investigate the effect of the aging process on the macula, fostering a better understanding of the pathophysiology of age-related macular diseases. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

NATURAL COURSE AND CLASSIFICATION OF EXTENSIVE MACULAR ATROPHY WITH PSEUDODRUSEN-LIKE APPEARANCE.

PURPOSE: To describe the imaging characteristics and topographic expansion of retinal pigment epithelium (RPE) and outer retinal atrophy in extensive macular atrophy with pseudodrusen-like appearance. METHODS: Three-year, prospective, observational study. Nine patients with extensive macular atrophy with pseudodrusen-like appearance (17 eyes; 6 women) with no other ocular conditions were annually examined; one eye was excluded because of macular neovascularization. Best-corrected visual acuity measurement, fundus photographs, blue-light autofluorescence, and optical coherence tomography were performed at each visit. Formation of atrophy was analyzed on optical coherence tomography at foveal and extrafoveal areas following the Classification of Atrophy Meeting recommendations. Spatial enlargement throughout four sectors was assessed on blue-light autofluorescence after placing an Early Treatment for Diabetic Retinopathy Study grid centered on the foveola. RESULTS: Mean age was 53.0 ± 2.1 years at baseline with a follow-up of 36.6 ± 0.7 months. Thinning of the outer nuclear layer and disruption of the ellipsoid zone initially appeared above areas of RPE-Bruch membrane separation and preceded RPE atrophy. Subfoveal fibrosis was seen in 65% of the eyes. Superior sector involvement was found in all patients at baseline and was significantly larger than the other sectors at any time point ( P < 0.001). Best-corrected visual acuity declined from 68.0 ± 15.7 letters to 44.8 ± 14.9 letters during the follow-up and was significantly associated with subfoveal atrophy ( P < 0.001) and fibrosis ( P = 0.02). CONCLUSION: Our findings suggest that primary alterations in patients with extensive macular atrophy with pseudodrusen-like appearance are present at the outer segment-RPE interface, with the superior Early Treatment for Diabetic Retinopathy Study sector being the most vulnerable, which progresses to extensive atrophy of the RPE and outer retinal layers. Accordingly, we propose a three-stage disease classification.

LONGITUDINAL FOLLOW-UP OF CHOROIDAL GRANULOMAS WITH INDOCYANINE GREEN ANGIOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY: A Lesion-Based Analysis.

PURPOSE: To investigate choroidal granulomas visualized by indocyanine green angiography (ICGA) and optical coherence tomography angiography (OCTA) in response to treatment. METHODS: Ten eyes of eight patients with tubercular, sarcoid, or Vogt-Koyanagi-Harada-associated choroidal granulomas were evaluated in this multicentric study. All patients underwent ICGA and OCTA at baseline, 1, and 3 months after treatment onset. Granulomas were identified as hypofluorescent lesions on intermediate ICGA phases. Late ICGA behavior and OCTA visualization were assessed. RESULTS: On baseline intermediate ICGA, 222 choroidal granulomas were detected. Overall, 174/222 granulomas were detected on baseline OCTA images. At 1 month, 28% of lesions were healed and 48 late ICGA hyperfluorescent lesions were identified. At 3 months, 63% of baseline lesions were healed, with 33 persistent late hyperfluorescent lesions. Optical coherence tomography angiography sensitivity was reduced at 1 and 3 months compared with baseline. Some flow-voids detected on OCTA at 1 and 3 months did not correspond to any visible lesion on ICGA. CONCLUSION: Different healing behaviors of choroidal granulomas were identified combining ICGA and OCTA analysis. Late ICGA hyper-fluorescent lesions may be the consequence of a possible fibrotic shift. Structural changes in the choroid may persist after active granulomas resolution resulting in persistent flow voids on OCTA.

Prechoroidal cleft thickness correlates with disease activity in neovascular age-related macular degeneration.

PURPOSE: The purpose of this study was to investigate the structural variations of the hyporeflective pocket of fluid (prechoroidal cleft) located between Bruch's membrane and the hyperreflective material within the pigment epithelial detachment (PED) in patients with neovascular age-related macular degeneration (nAMD). METHODS: In this retrospective, observational case series study, patients diagnosed with nAMD and prechoroidal cleft associated with other activity signs of the macular neovascularization (MNV) were included. Structural optical coherence tomography (OCT) scans were evaluated to obtain anatomical measurements of prechoroidal cleft and PED at three different visits (T0, inactive MNV; T1, active MNV; T2, treated inactive MNV). The variations in size of the cleft and the PED were correlated with nAMD activity. RESULTS: Twenty-nine eyes from 27 patients were included. The subfoveal measurements showed a significant increase of prechoroidal cleft height and width from T0 to T1 (P < 0.05) and a subsequent decrease of the cleft height after treatment with anti-VEGF agents (P = 0.004). A similar significant trend was observed for the greatest prechoroidal cleft height and width, obtained assessing the whole OCT raster. In the multivariate analysis, the cleft height was significantly affected by both time (P = 0.001) and PED height (P < 0.0001). By contrast, the effect of fibrovascular tissue size within the PED was not significant. Visual acuity did not correlate with prechoroidal cleft size. CONCLUSION: Prechoroidal cleft increased in association with MNV reactivation and decreased after treatment. Our results suggest that prechoroidal cleft could represent an accumulation of fluid actively exudating from the MNV and should be considered a sign of nAMD activity.

Intravitreal injection associated rhegmatogenous retinal detachment: outcomes of a European analysis.

PURPOSE: As the number of intravitreal injections (IVI) increases annually, this study aimed to assess the anatomical and functional outcomes following rhegmatogenous retinal detachment (RRD) surgery for IVI-associated RRD (IVARD). METHODS: All non-vitrectomized eyes developing IVARD since 2007 in two European vitreoretinal centers (Department of Ophthalmology, LMU Munich, Germany, and Eye Clinic Luigi Sacco, University of Milan, Milan, Italy) were included. Main outcomes were primary and secondary retinal attachment rate after surgery, rate of proliferative vitreoretinopathy (PVR), and final functional result. Ten years of incidence rates per injection were calculated for one center. RESULTS: Fifty-two eyes of 52 patients comprised the study. Primary anatomic success rate was 83% (n = 43) and secondary 96% (n = 50). PVR was observed in all uveitic eyes (n = 3), in eyes with postoperative cystoid macular edema (n = 2), and in 8 of 9 eyes that received the dexamethasone implant (DEX). Age, number of prior injections, duration of symptoms, or time between last IVI and RRD did not show any statistically significant differences with regard to presence of PVR or not. Mean BCVA improved in 28 cases, remained stable in 16 cases, and worsened in 8 cases. The RRD incidence rate was statistically significant higher for DEX and ocriplasmin compared with that for anti-VEGF agents. CONCLUSION: The anatomical result after one surgical intervention seems acceptable, but the final visual outcome remains rather poor, because of the underlying macular disease. In our population, injection with DEX is associated with higher IVARD rate, presence and development of PVR, and recurrent RRD in comparison with anti-VEGF agents.

Outer Retinal Layer Thickening Predicts the Onset of Exudative Neovascular Age-Related Macular Degeneration.

PURPOSE: To assess changes in outer retinal layer (ORL) thickness before the development of exudative macular neovascularization (MNV) in eyes with age-related macular degeneration. DESIGN: Retrospective observational case series. METHODS: Eyes with age-related macular degeneration that eventually developed exudative MNV followed with sequential optical coherence tomography for ≥2 years before the exudation occurred were enrolled. The ORL thickness was automatically calculated by the optical coherence tomography software for each sector of the early treatment diabetic retinopathy study map at each follow-up visit. The ORL thickness change from baseline to the day when the exudative MNV developed was compared between sectors that eventually developed exudative MNV and those that did not. RESULTS: Forty-seven eyes (47 patients) were included. At baseline (24 ± 3 months before exudative MNV), mean (standard deviation) ORL thickness of sectors that eventually developed exudative MNV was similar to that of sectors that did not (85.2 [8.2] µm vs 86.8 [5.7] µm, P = .08). ORL thickness significantly increased in sectors that developed exudative MNV compared with those that did not (+5.8 [10.4] µm vs -2.8 [3.6] µm, P < .01). The regression model based on these data predicted an increase in ORL thickness from baseline of +4.2% 55 days and +11.1% 30 days before exudative MNV was detected. The ORL thickness of areas that did not develop exudative MNV did not change. CONCLUSION: Thickening of the ORL begins in the area where exudative MNV will develop long before the exudation, accelerating significantly in the last 2 months. The occurrence of exudative MNV could be predicted by 2 months using this simple analysis.

Comparison between Widefield Optical Coherence Tomography Devices in Eyes with High Myopia.

BACKGROUND: To compare four different optical coherence tomography (OCT) devices for visualization of retinal and subretinal layers in highly myopic eyes. METHODS: In this prospective, observational, cross-sectional study, consecutive patients with high myopia and control subjects were imaged by four OCT devices: Spectralis OCT2, PlexElite 2.0 100 kHz, PlexElite 2.0 200 kHz and the Canon Xephilio OCT-S1. The acquisition protocol for comparison consisted of single vertical and horizontal line scans centered on the fovea. Comparison between the devices in the extent of visible retina, presence of conjugate image or mirror artifacts, visibility of the sclerochoroidal interface and retrobulbar tissue. RESULTS: 30 eyes with high myopia and 30 control subjects were analyzed. The visualized RPE length was significantly different between the OCT devices with Xephilio OCT-S1 imaging the largest extent (p < 0.0001). The proportion of eyes with conjugate image artifact was significantly higher with the Spectralis OCT (p < 0.0001), and lower with the PlexElite 200 kHz (p < 0.0001). No difference in visibility of the sclerochoroidal interface was noted among instruments. The retrobulbar tissue was visible in a higher proportion of eyes using swept-source PlexElite 100 kHz and 200 kHz (p < 0.007) compared to the other devices. CONCLUSIONS: In highly myopic eyes, the four OCT devices demonstrated significant differences in the extent of the retina imaged, in the prevalence of conjugate image artifact, and in the visualization of the retrobulbar tissue.

Microaneurysms visualisation using five different optical coherence tomography angiography devices compared to fluorescein angiography.

BACKGROUND: To compare fluorescein angiography (FA) and five different optical coherence tomography angiography (OCTA) devices and to test their reproducibility in the evaluation of retinal microaneurysms (MAs) secondary to diabetic retinopathy (DR). METHODS: On the same day, patients with DR were imaged with FA and five OCTA devices: prototype Spectralis OCTA, prototype PlexElite, RTVue XR Avanti, AngioPlex and DRI OCT Triton. For all OCTA devices, a 3×3 volume scan pattern was performed. MAs were evaluated for the superficial capillary plexus (SCP) and deep capillary plexus (DCP). RESULTS: Twenty eyes of 15 patients with DR were included. FA counted a significantly higher number of MAs compared to OCTA devices. Spectralis OCTA obtained a significantly higher number of MAs compared to PlexElite, RTVue XR Avanti, AngioPlex and DRI OCT Triton (p<0.0001). PlexElite and AngioPlex showed a greater number of MAs in the SCP, Spectralis OCTA, RTVue XR Avanti and DRI OCT Triton in the DCP. Higher sensitivity (43.3%) but lowest specificity (54.4%) was observed for Spectralis OCTA compared to other devices. The higher specificity (78.5%) and positive predictive value (83.3%) were observed for DRI OCT Triton. CONCLUSIONS: FA remains the best imaging modality to visualise retinal MAs. Spectralis OCTA was able to detect more MAs compared to other devices, likely due to the higher number of B-scans in the scanned area as well as due to the higher number of repeated B-scans. The high variability between OCTA devices should be taken into account for future clinical trials as in clinical practice.

Sensitivity and Specificity of Multimodal Imaging in Characterizing Drusen.

PURPOSE: To calculate the measures of accuracy of different imaging modalities in patients with early/intermediate age-related macular degeneration (AMD). DESIGN: Prospective, observational, cross-sectional study. PARTICIPANTS: Patients with early or intermediate AMD. METHODS: All participants underwent a complete multimodal imaging assessment with a confocal scanning laser ophthalmoscope, including near-infrared reflectance (NIR), green fundus autofluorescence (G-FAF), confocal pseudocolor, and retromode deviated to right (DR) and left (DL). Drusen were topographically divided as small and medium (≤125 µ diameter) and large (>125 µ diameter), whereas subretinal drusenoid deposits (SDDs) were divided into dot and ribbon phenotypes. Multimodal imaging was considered the reference standard for detecting different subtypes of drusen and SDDs. Cohen's kappa (k) was used to test interobserver agreement for each imaging modality. MAIN OUTCOME MEASURES: Capability to differentiate subtypes of drusen and SDDs with different imaging modalities. RESULTS: A total of 100 eyes (62% were female participants) were evaluated. The inter-rate reliability between 2 readers for each imaging modality ranged between 0.76 and 0.95. Overall, large drusen were better identified with confocal pseudocolor imaging (96.6% sensitivity; 77.8% specificity). Smaller drusen were better detected with retromode modalities DR or DL (92% sensitivity; 58.3% specificity and 85.2% sensitivity; 83.3% specificity, respectively). Ribbon SDDs were better detected by color imaging (80.5% sensitivity; 98.3% specificity). Dot SDDs were well identified with NIR (83.1% sensitivity; 91.4% specificity) and G-FAF (84.6% sensitivity; 77.1% specificity). CONCLUSIONS: Near-infrared reflectance and G-FAF should be considered for classification of dot SDDs, and confocal pseudocolor is optimal for characterizing ribbon SDDs. Among all imaging modalities, retromode technology DR and DL may be a potential supplementary modality to detect even smaller drusen.

Macular Atrophy Incidence and Progression in Eyes with Neovascular Age-Related Macular Degeneration Treated with Vascular Endothelial Growth Factor Inhibitors Using a Treat-and-Extend or a Pro Re Nata Regimen: Four-Year Results of the MANEX Study.

PURPOSE: To compare the incidence and progression of macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents using either a treat-and-extend (T&E) or a pro re nata (PRN) regimen over 4 years in a real-world setting. DESIGN: Four-year, multicenter, retrospective comparative study. PARTICIPANTS: Two hundred sixty-four patients with treatment-naive nAMD. METHODS: Consecutive patients with nAMD received anti-VEGF therapy according to a T&E (n = 163) or PRN (n = 101) regimen. Eyes were included if they had received anti-VEGF injections for a period of at least 4 years and had undergone annual fundus autofluorescence (FAF) and OCT imaging using Heidelberg Spectralis. Two masked graders independently delineated areas of MA from serial FAF images using Heidelberg region finder software, and growth rates were calculated. Incident MA was assessed using proportional hazard ratios. MAIN OUTCOMES MEASURES: Macular atrophy incidence and progression over 4 years, association between treatment strategies, and number of injections. RESULTS: At baseline, MA was present in 24% and 20% of study eyes in T&E and PRN groups, respectively (P = 0.45). At year 4, 27% (34/124) and 25% (20/81) of eyes without baseline MA showed detectable MA in the T&E and PRN groups, respectively. In those with MA at baseline, the mean square root area of MA progressed by a rate of 0.4 ± 0.2 mm/year and 0.4 ± 0.1 mm/year in the T&E and PRN groups, respectively (P = 0.23). Multivariate analysis for baseline predictors of MA growth demonstrated that older age, poorer baseline visual acuity, and presence of retinal angiomatous proliferation had a higher risk of greater MA progression (P = 0.03). Regression analysis demonstrated no association between T&E and PRN treatment strategies with the risk of new MA developing during the 4 years of follow-up or the progression of pre-existing MA at year 4 (P = 0.692). CONCLUSIONS: Over 4 years, neither incidence nor progression of MA in eyes with nAMD treated with anti-VEGF injections was influenced by the treatment regimen and injection frequency. Eyes treated with a T&E regimen received more injections and achieved better visual outcomes compared with those treated with a PRN approach.

Needle revision outcomes after glaucoma filtering surgery: survival analysis and predictive factors.

PURPOSE: To evaluate the efficacy and safety of needle revision and examine factors predictive of failure. METHODS: In total, 157 eyes of 131 patients that underwent needle revision augmented with either 5-fluorouracil or betamethasone for trabeculectomy failure were included in this retrospective study. Complete failure was defined as additional glaucoma surgery, ciliodestructive procedures, loss of light perception, sight-threatening complications, hypotony maculopathy, and surgical bleb revision. Success was defined as intraocular pressure ⩽ 18 (criterion A), ⩽15 (criterion B), and ⩽12 mmHg (criterion C) reached with (qualified) or without (complete) medications, and absence of any criteria of complete failure. RESULTS: The median (interquartile range) follow-up was 25.0 (41.0) months. Complete failure rates were 19%, 26%, and 31% at 1, 2, and 3 years, respectively. For criterion A, qualified and complete success rates were, respectively, 77% and 69% at 1 year, 66% and 51% at 2 years, and 60% and 47% at 3 years. For criterion B, qualified and complete success rates were, respectively, 67% and 61% at 1 year, 48% and 42% at 2 years, and 44% and 39% at 3 years. For criterion C, qualified and complete success rates were, respectively, 43% and 41% at 1 year, 27% and 25% at 2 years, and 24% and 23% at 3 years. High baseline intraocular pressure and primary surgery were associated with higher and lower risks of complete failure, respectively. CONCLUSION: Needle revision is an effective and safe procedure to rescue failing trabeculectomy postponing or avoiding further glaucoma surgery. Eyes with low target intraocular pressure may have poor long-term outcomes.

Impact of combined hormonal contraceptives on vessels functionality.

PURPOSE: To evaluate the dynamic and static retinal vascular functionality in young females using combined hormonal contraceptive (CHC). METHODS: Thirty-eight consecutive young female subjects were enrolled in this study between January 2015 and December 2015. Subjects were divided in two groups: CHC group, defined as CHC use for ≥6 months, and control group, defined as no current and prior CHC use. Participants underwent a dynamic and static retinal vessel analysis using the Dynamic Vessel Analyzer (DVA, Imedos, Jena, Germany). RESULTS: Seventeen subjects continuously took CHC for 54.6 ± 29.3 months, while 21 subjects belonged to control group. No difference was found between the CHC and control groups for age (p = 0.1), smoking status (p = 0.6), and systolic (p = 0.3) and diastolic (p = 0.1) blood pressure. With regard to dynamic analysis, women taking CHC exhibited a marked significant vasoconstriction following flicker stimulation in comparison with control group (-2.43 ± 2.5 vs 0.63 ± 2.1, respectively; p = 0.0002). No significant difference was observed between groups for mean arterial (p = 0.2) and venous dilatations (p = 0.3), arteriovenous ratio (p = 0.09), central retinal artery equivalent (p = 0.4), and central retinal venous equivalent (p = 0.5). CONCLUSIONS: CHC may affect vessel reactivity to flicker light by increasing arteries constriction. This may reflect systemic changes in vascular functionality in subjects using CHC. Moreover, CHC should be considered as a confounding bias in studies involving DVA.