Retinal and choroidal vasoreactivity in central serous chorioretinopathy.

PURPOSE: This study aims to investigate retinal and choroidal vascular reactivity to carbogen in central serous chorioretinopathy (CSC) patients. METHODS: An experimental pilot study including 68 eyes from 20 CSC patients and 14 age and sex-matched controls was performed. The participants inhaled carbogen (5% CO2 + 95% O2) for 2 min through a high-concentration disposable mask. A 30° disc-centered fundus imaging using infra-red (IR) and macular spectral domain optical coherence tomography (SD-OCT) using the enhanced depth imaging (EDI) technique was performed, both at baseline and after a 2-min gas exposure. A parametric model fitting-based approach for automatic retinal blood vessel caliber estimation was used to assess the mean variation in both arterial and venous vasculature. Choroidal thickness was measured in two different ways: the subfoveal choroidal thickness (SFCT) was calculated using a manual caliper and the mean central choroidal thickness (MCCT) was assessed using an automatic software. RESULTS: No significant differences were detected in baseline hemodynamic parameters between both groups. A significant positive correlation was found between the participants' age and arterial diameter variation (p < 0.001, r = 0.447), meaning that younger participants presented a more vasoconstrictive response (negative variation) than older ones. No significant differences were detected in the vasoreactive response between CSC and controls for both arterial and venous vessels (p = 0.63 and p = 0.85, respectively). Although the vascular reactivity was not related to the activity of CSC, it was related to the time of disease, for both the arterial (p = 0.02, r = 0.381) and venous (p = 0.001, r = 0.530) beds. SFCT and MCCT were highly correlated (r = 0.830, p < 0.001). Both SFCT and MCCT significantly increased in CSC patients (p < 0.001 and p < 0.001) but not in controls (p = 0.059 and 0.247). A significant negative correlation between CSC patients' age and MCCT variation (r = - 0.340, p = 0.049) was detected. In CSC patients, the choroidal thickness variation was not related to the activity state, time of disease, or previous photodynamic treatment. CONCLUSION: Vasoreactivity to carbogen was similar in the retinal vessels but significantly higher in the choroidal vessels of CSC patients when compared to controls, strengthening the hypothesis of a choroidal regulation dysfunction in this pathology.

Central serous chorioretinopathy and angioid streaks: coincidental?

BACKGROUND: To report an unusual case of central serous chorioretinopathy in a patient with angioid streaks. CASE PRESENTATION: The authors describe a case report of a 26-year old male patient presenting acute scotoma and metamorphopsia in OD. He had been diagnosed with angioid streaks complicated with choroidal neovascularization and referred to us for treatment. The patient presented an ETDRS score of 85 letters (20/20) in OD and in OS. The anterior segment examination was unremarkable. Fundoscopy revealed bilateral angioid streaks (AS) and peau d'orange, as well as a small neurosensory retinal detachment in the macula of OD. A multimodal retinal analysis, including fundus photography, infra-red and fundus autofluorescence imaging, spectral-domain optical coherence tomography, optical coherence tomography angiography, fluorescein and indocyanine green angiography was performed. The diagnosis of central serous chorioretinopathy was made in the absence of any identifiable choroidal neovascularization. He was submitted to half-dose photodynamic therapy with verteporfin. One month later, he reported no visual complaints, his vision was 85 letters (20/20) in OD and a complete resolution of the sub-retinal fluid was registered. No signs of choroidal neovascularization were detected on the optical coherence tomography angiography (OCTA). A complete medical workup evaluation was made to exclude systemic diseases usually associated with AS. CONCLUSIONS: To the authors' knowledge, this is the second reported case of CSC associated with angioid streaks. The focal abnormalities in the Bruch's membrane and the irregular vascular choriocapillary network associated with AS might predispose to CSC.

Prevalence and Area of Retinal Pigment Epithelium and Outer Retinal Atrophy in Eyes with Non-Exudative Macular Neovascularization.

PURPOSE: The objective of this study wasto assess the prevalence of complete retinal pigment epithelium (RPE) and outer retinal atrophy (cRORA) in patients with unilateral exudative age-related macular degeneration (AMD) of the fellow eye and establish if the presence of non-exudative macular neovascularization (NE-MNV) influences the prevalence of RPE and outer retinal atrophy in eyes with AMD. METHODS: This is an observational cross-sectional study of 68 patients with unilateral exudative AMD. Demographic and clinical data were collected, and multimodal retinal imaging was performed in all patients. Two groups of patients were defined according to the presence (NE-MNV) or absence (no NE-MNV) of NE-MNV in the study eye. We compared the prevalence of tomographic cRORA and fundus autofluorescence (FAF) geographic atrophy (GA) and differences in cRORA greatest linear diameter (GLD) and GA area between groups. RESULTS: Globally, cRORA was present in 11 eyes (16.2%), FAF GA was present in 10 eyes (14.7%), and NE-MNV was present in 10 eyes (14.7%) of patients with unilateral exudative AMD of the fellow eye. The overall cRORA GLD was 1,950.64 ± 1,428.31 µm, and the mean area of GA was 9.25 ± 7.50 mm2. Regarding comparisons between groups, cRORA was present in 9 eyes (15.5%) without NE-MNV and in 2 eyes (20%) with NE-MNV (p = 0.66). Tomographic signs of atrophy were more frequent in eyes with NE-MNV (50% vs. 24.1% in eyes without NE-MNV; p = 0.008). No significant differences were found in cRORA GLD (p = 0.30) between groups. Eyes with NE-MNV and eyes without NE-MNV had a similar prevalence of FAF GA (2 eyes out of 10 and 8 eyes out of 58, respectively; p = 0.64). Eyes with NE-MNV had a smaller mean area of GA (2.07 ± 0.24 mm2 vs. 11.05 ± 7.34 mm2; p = 0.01). CONCLUSION: In our study, the presence of NE-MNV was not associated with the prevalence of cRORA and/or FAF GA. Nonetheless, eyes with NE-MNV presented smaller areas of GA, which suggests that this type of neovascularization may prevent the progression of RPE and outer retinal atrophy. Longitudinal studies are required to confirm these preliminary results.

Quantitative Optical Coherence Tomography Angiography Biomarkers for Alport Syndrome.

PURPOSE: The aim of this study was to evaluate microvascular abnormalities of patients with Alport syndrome (AS) using optical coherence tomography angiography (OCT-A) quantitative biomarkers. METHODS: This was cross sectional, prospective evaluation of consecutive patients with AS and healthy subjects. AS diagnosis was performed by the genetic test. All participants underwent a retinal vasculature evaluation by spectral-domain optical coherence tomography (SD-OCT) and OCT-A of the macula. Quantitative analysis included whole vascular density, foveal avascular zone area, fractal dimension (FD), and lacunarity (LAC). RESULTS: Ninety-four eyes were included in this study, 45 eyes from patients with AS and 49 eyes from healthy subjects. The pathogenic mutation in the COL4A5 gene on the chromosome X was found in 14 patients; the pathogenic autosomal recessive mutations in the COL4A3 gene were found in 9 patients. Quantitative evaluation demonstrated a significant difference between AS and healthy subjects on LAC of the superficial capillary plexus and deep capillary plexus (DCP) (p < 0.001 and p < 0.001, respectively) and on FD in the DCP (p < 0.001). CONCLUSION: The DCP Alport patients have a higher vessel nonuniformity than DCP of healthy subjects. We hypothesize that endothelial cell lesion in the setting of low resistance at the DCP circuit could lead to long-term structural disorganization.

Cerebral Neurovascular Coupling Impairment in Central Serous Chorioretinopathy.

BACKGROUND: Central serous chorioretinopathy (CSCR) is a chorioretinal disorder resulting from choroidal hyperpermeability. Its comorbidities as hypertension, coronary disease, and psychological stress, suggest that it might reflect a more generalized vascular dysfunction. OBJECTIVES: The aim of the study was to assess the cerebrovascular regulation integrity, using cerebral autoregulation (CA), carbon dioxide vasoreactivity (VR), and neurovascular coupling (NVC) in CSCR. METHODS: This observational pilot study included 20 CSCR patients and 14 age- and sex-matched controls. A State-Trait Anxiety Inventory (STAI) inquiry was full-filled. Continuous measurement of cerebral blood flow velocity (CBFV), arterial blood pressure, heart rate, and end-tidal carbon dioxide was performed. VR was assessed during hypercapnia (inhaling carbogen gas) and hypnocapnia (hyperventilation). For NVC, the CBFV relative increase during mental activation using the N-Back Task was calculated. RESULTS: No significant differences in systemic hemodynamic parameters, CA or VR, were found between both groups. During the NVC performance, the average CBFV rise during mental stress was significantly lower in CSCR (p = 0.011). A significant negative correlation was found between STAI scores and NVC. CONCLUSIONS: CSCR patients presented a significantly impaired cerebral NVC compared to controls, supporting the theory of a potential systemic vascular dysfunction. Stress could be related to this NVC impairment.

Efficacy and Safety of Intravitreal Aflibercept Treat and Extend for Polypoidal Choroidal Vasculopathy in the ATLANTIC Study: A Randomized Clinical Trial.

IMPORTANCE: Polypoidal choroidal vasculopathy (PCV) is far less common and studied in a Caucasian population than in an Asian population, and the optimal treatment approach remains to be confirmed. METHODS: A 52-week, double-masked, sham-controlled, phase 4, investigator-initiated randomized clinical trial (RCT) in naive symptomatic Caucasian patients with PCV treated with aflibercept in a treat-and-extend regimen (T&E) (intravitreal aflibercept injection [IVAI] T&E). Patients were randomized at week 16 to receive IVAI T&E plus either sham photodynamic therapy (PDT) or standard fluence PDT with verteporfin. The main outcome measures were changes in best-corrected visual acuity (BCVA) from baseline to 52 weeks and polyp occlusion at week 52. Data are presented as median (interquartile range [IQR]) for BCVA, number of IVAI, and change in central retinal thickness (CRT). RESULTS: Of the 50 patients included in the study, 48 patients completed the 52 weeks of follow-up. During this period, a significant median (IQR) BCVA gain of 6 [2-12] Early Treatment Diabetic Retinopathy Study letters was observed for all patients (p < 0.001), after 8 (7-9) injections, with a significant reduction of -93.0 [-154.0, -44.0] µm in central macular thickness (p < 0.001). Using indocyanine green angiography, a complete occlusion of polypoidal lesions was documented in 72% of the cases. Still, no significant difference was detected between the sham PDT and the aflibercept PDT arms, at week 52, for BCVA change (6.5 [2-11] vs. 5 [2-13] letters (p = 0.98)), number of IVAIs (8.5 [7-9] vs. 8 [7-9] (p = 0.21)), change in CRT (-143 [-184; -47] vs. -89 [-123; -41.5] µm [p = 0.23]), and rates of complete polyp occlusion: 77 versus 68% (p = 0.53) or presence of fluid: 68 versus 57% (p = 0.56). No serious ocular adverse events were registered in the 2 arms. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first RCT to compare aflibercept T&E monotherapy with aflibercept T&E plus verteporfin PDT in a Caucasian population with PCV. Aflibercept monotherapy in a T&E showed to be effective and safe with a significant median BCVA improvement of 6 letters and a complete occlusion of polypoidal lesions in near 3 quarters of the eyes, at 1 year. As only 22% of the eyes underwent PDT treatment, the benefit of combined treatment for PCV in Caucasian patients could not be definitively elucidated from this study. TRIAL REGISTRATION: The clinical trial was registered in ClinicalTrials.gov Identifier NCT02495181 and the European Union Drug Regulating Authorities Clinical Trials Database EudraCT No. 2015-001368-20.

Challenges to the provision of specialized care in remote rural municipalities in Brazil.

This case study analyses the challenges to providing specialized care in Brazilian remote rural municipalities (RRM). Interviews were conducted with managers from two Brazilian states (Piauí and Bahia). We identified that the distance between municipalities is a limiting factor for access and that significant care gaps contribute to different organizational arrangements for providing and accessing specialized care. Physicians in all the RRMs offer specialized care by direct disbursement to users or sale of procedures to managers periodically, compromising municipal and household budgets. Health regions do not meet the demand for specialized care and exacerbate the need for extensive travel. RRM managers face additional challenges for the provision of specialized care regarding the financing, implementation of cooperative arrangements, and the provision of care articulated in networks to achieve comprehensive care, seeking solutions to the locoregional specificities.

A Delphi study on the clinical management of age-related macular degeneration.

PURPOSE: Age-related macular degeneration (AMD) is one of the main causes of blindness and visual impairment worldwide. As achieving a dry macula is one of the main objectives in AMD management, the purpose of this work was to reach a consensus on the relevance of retinal fluid in function, disease activity control and treatment patterns. METHODS: Forty-seven Portuguese ophthalmologists specialized in AMD participated in a DELPHI panel. Two rounds of presential meetings were conducted and a cut-off of 80% or more of votes was defined to consider answers consensual. RESULTS: Consensus was reached for 11 out of 18 questions. These questions focused on the impact of anatomical results on visual acuity, standards exams and parameters to assess disease activity, frequency and factors which influence disease activity assessment, criteria to use non-fixed treatment regimens, usefulness of individualized regimens and conditions for treatment interruption. No consensus was obtained for relevance of the different fluid types in AMD prognosis, frequency of fluid presence assessment, factors commonly associated with progression to geographic atrophy, ideal conditions for a fixed treatment regimen, date of first disease activity assessment and parameters to monitor disease activity. CONCLUSIONS: Consensus was achieved for over half of the questions assessed through this Delphi study. The questions for which no consensus was reached concerned either subjects that need further investigation or monitoring times which are influenced by resource availability. Raising awareness for these issues will allow the improvement of AMD management and treatment.

Long-term progression of geographic atrophy in age-related macular degeneration does the phakic status matter?

PURPOSE: To assess the long-term risk of geographic atrophy (GA) progression after cataract surgery. METHODS: Subjects with GA secondary to AMD followed for at least 1 year with fundus autofluorescence imaging and with at least two visits at our centre were included. Patients with wet AMD, disciform scar, past history of intravitreal injections or laser treatment, other maculopathies and with poor quality images were excluded. GA area at baseline and at follow-up visit was measured. Three study groups were defined according to their phakic status: (A) pseudophakia, (B) phakic and (C) phacoemulsification surgery performed during the study. Differences of GA area progression were compared between these study groups. In addition, comparison between GA progression rate in group (C) before and after the surgery was performed. The enlargement rate (ER) was calculated for lesion size after transforming the measurements to the square-root scale. RESULTS: A total of 92 eyes of 92 patients were enrolled. Median follow-up time was 4 [1-10] years. Regarding the eye's phakic status, 29 (31.5%) were pseudophakic and 63 (68.5%) were phakic; of these, 22 underwent phacoemulsification during the study. Overall, the median baseline and follow-up area of GA were 1.42 [0.04-32.10] mm2 and 6.48 [0.25-47.40] mm2, respectively. The ER was similar between phakic and pseudophakic eyes (0.18 [0.01-1.03] vs 0.15 [0.01-0.65] mm/year, p = 0.62). In patients that underwent cataract surgery during the study, the GA ER remained stable (0.13 [0.01-0.92] vs 0.14 [0.01-0.63] mm/year, p = 0.43). CONCLUSION: These results suggest that cataract surgery does not increase the risk of pre-existing GA progression. Therefore, cataract surgery seems safe and a potential therapeutic weapon to improve visual acuity and consequently quality of life in GA patients.

Predicting retinal pigment epithelium remodelling and its functional impact.

PURPOSE: To identify predictive factors for RPE tear remodelling and its correlation with functional and morphological outcomes. METHODS: Retrospective longitudinal study of patients with retinal pigment epithelium (RPE) tears secondary to age-related macular degeneration (AMD). Imaging was performed using spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF). RPE layer integrity in the RPE-denuded area was examined with SD-OCT, and variation in the RPE-denuded homogeneous hypofluorescent area was examined with FAF over time for each case (eye). Patients were divided in two groups, according to the presence (Rem) or absence (No Rem) of evidence of RPE tear remodelling. Data were collected at three different time points: at baseline (at diagnosis of exudative AMD), at RPE tear diagnosis, and at the last available follow-up. Using SD-OCT, the following parameters were evaluated: type of CNV, type of PED and its dimensions, presence of subretinal (SRF) or intraretinal (IRF) fluid, central retinal thickness (CRT), presence and location of hyperreflective dots, and dimension and location of RPE tear. RESULTS: This study included 32 eyes from 31 patients (19 female and 12 male), with RPE tears secondary to AMD. RPE remodelling after tear development was evident in 17 (53.1%) eyes after 7 [1-59] months. Anatomical recovery was associated with a younger age at RPE tear diagnosis (73 ± 7 vs. 81 ± 7 years old, p=0.01), smaller and narrower retinal pigment epithelial detachment (PED) at tear diagnosis (height 369 vs. 602 µm, p=0.02; width 2379 vs. 3378 µm, p=0.04), and the presence of SRF at tear diagnosis (94% vs. 53%, p=0.02). After adjusting for other covariates, a younger age at RPE tear diagnosis maintained significant association with RPE tear remodelling. RPE tear remodelling did not correlate with a better visual outcome at last follow-up (43 ± 22.8 vs. 34 ± 23.8 ETDRS letters, p=0.30). Final VA was directly proportional to VA at tear diagnosis (r= 0.654; p<0.001) and correlated negatively with PED width at tear diagnosis (r = -0.388; p=0.03). CONCLUSION: RPE remodelling was evident in half of our sample and was associated with a younger age, smaller and narrower PED at RPE tear diagnosis, and presence of SRF also at tear diagnosis. Nevertheless, this structural recovery did not result in a better functional outcome.

CORRELATION STUDY BETWEEN DRUSEN MORPHOLOGY AND FUNDUS AUTOFLUORESCENCE.

PURPOSE: To correlate drusen morphology and outer retinal status with autofluorescence (AF) imaging in patients with intermediate age-related macular degeneration. METHODS: Drusen type and morphology were analyzed using color fundus photography and spectral-domain optic coherence tomography, whereas fundus AF was used for drusen AF evaluation. Additional structural changes on spectral-domain optic coherence tomography, such as disruption of external limiting membrane, ellipsoid zone, and retinal pigment epithelium/Bruch membrane complex, as well as the presence of choroidal hypertransmission at correspondent locations were also evaluated and correlated with fundus AF findings. Spearman's correlation coefficient was used to analyze the correlation between spectral-domain optic coherence tomography morphological characteristics of drusen and AF appearance of the corresponding drusen. Strength of correlation was calculated (r), and a P value < 0.05 was considered statistically significant. RESULTS: Two hundred and twenty-eight drusen from 53 eyes of 53 patients were analyzed, 130 soft drusen (57.02%) and 98 cuticular drusen (42.98%). Sixty percent of the drusen were isoautofluorescent (n = 136), 35% hyperautofluorescent (n = 80), and 5% hypoautofluorescent (n = 12). We found positive correlation between drusen AF and hyperreflective foci (r = 0.4). Outer retinal layers morphology (external limiting membrane and ellipsoid zone status and hypertransmission) also correlates with autofluorescent findings (r = 0.3). CONCLUSION: Multimodal imaging reveals a broad spectrum of ultrastructural changes, which may reflect different stages in the evolution of drusen. Our results suggest that drusen morphological characteristics and autofluorescent findings are correlated but other factors or cofactors may be involved. The described correlations will help us understand new progression biomarkers of nonexudative age-related macular degeneration.

Age-Related Macular Degeneration: Pathophysiology, Management, and Future Perspectives.

Among older adults, age-related macular degeneration (AMD) is a prevalent disabling condition that begins as subtle visual disturbances and can progress to permanent loss of central vision. In its late neovascular form, AMD is treatable with inhibitors of vascular endothelial growth factor, the key driver of exudative disease. In the atrophic form, treatment remains elusive. This review addresses the natural history of AMD - through early, intermediate, and advanced disease stages - and concentrates on diagnosis and risk stratification, deficiencies of current treatments, and the promising findings of emerging therapies.

Longitudinal Retinal Changes Induced by Hydroxychloroquine in Eyes without Retinal Toxicity.

INTRODUCTION: This study aimed to evaluate the longitudinal changes in retinal layer thickness in patients treated with hydroxychloroquine without retinal toxicity. METHODS: This is a longitudinal retrospective study of patients taking hydroxychloroquine followed in a hydroxychloroquine retinal toxicity screening program of a tertiary hospital between January 2010 and April 2019. Patients who performed 2 optical coherence tomography (OCT) scans at least 1 year apart were included. All subjects with hydroxychloroquine suspected or confirmed retinal toxicity, glaucoma, retinal pathology, or poor segmented images were excluded. Spectral-domain optical coherence tomography (Spectralis HRA-OCT, Heidelberg) was used to evaluate the macular area. Automatically segmented ETDRS retinal thickness maps were compared between the first and the last OCT evaluation available. Full retina (FR), inner retina (IRL), ganglion cells (GCL), inner nuclear (INL), and outer retina (ORL) layer thicknesses were measured in the foveolar, paracentral, and peripheral area. RESULTS: The population included 144 eyes of 144 patients. The mean interval between OCT scans was 38.1 ± 18.4 months, and the mean cumulative dose was 406.9 ± 223.9 g. Foveolar (p = 0.040, p = 0.006, and p = 0.001, respectively) and paracentral (p = 0.006, p = 0.001, and p = 0.005, respectively) FR, IRL, and GCL decreased overtime. No differences were found in INL or ORL. A very weak correlation was found between age and foveal IRL change overtime (p = 0.037; R = 0.175), as well as between the hydroxychloroquine time of use and foveal GCL variation (p = 0.032; R = 0.179). CONCLUSION: Hydroxychloroquine was found to cause progressive thinning of the inner retinal layers, specifically in the GCL of the foveolar and paracentral areas, but no changes were observed in the outer retina.

Clinical Characteristics of the Charles Bonnet Syndrome in Patients with Neovascular Age-Related Macular Degeneration: The Importance of Early Detection.

PURPOSE: We investigated the characteristics, prognosis, and clinical outcome of the Charles Bonnet syndrome (CBS) in patients with neovascular age-related macular degeneration (AMD). METHODS: Five hundred psychiatrically healthy patients with neovascular AMD were screened for CBS. The individuals that fulfilled the inclusion criteria were systematically interviewed using a structured questionnaire that covered the impact, prognosis, risk factors, phenomenology, symptoms, and knowledge about the syndrome. A control group of 45 patients was used for comparison. Demographic data, current medication, and ocular risk factors were collected in all patients. RESULTS: Forty-five patients with CBS were identified. The majority of patients reported images that consisted of colored (62%) animals (44%) or faces (42%) that lasted for seconds (53%). Most patients reported a self-limited disease with a median duration of symptoms between 9 and 11.5 months, with only 7% knowing about CBS at symptom onset. The degree of visual deficit did not predict the characteristics, complexity, frequency, duration, or impact of visual hallucinations. One-third of patients reported negative outcome, which was associated with shorter duration of CBS (p = 0.023), fear-inducing images (p < 0.001), and impact on daily activities (p = 0.015). CONCLUSION: The prevalence of CBS in neovascular AMD patients is high and clinically relevant. Patients with recent onset of visual hallucinations and describing fear-inducing images are at greater risk for negative outcome. Periodic screening may minimize the negative consequences of this disease.

Aflibercept in diabetic macular edema refractory to previous bevacizumab: outcomes and predictors of success.

PURPOSE: To evaluate functional and anatomical outcomes after aflibercept in patients with diabetic macular edema (DME) with poor response to bevacizumab. METHODS: We retrospectively reviewed patients with DME recalcitrant to bevacizumab who were switched to aflibercept between January and December 2015. All patients had a minimal follow-up of three months before the conversion and underwent at least three injections of bevacizumab. Functional outcome consisted in best corrected visual acuity (VA). Anatomical outcomes were demonstrated through central macular thickness (CMT) measured by optical coherence tomography. RESULTS: Forty-nine eyes of 34 subjects were reviewed. Mean VA improved from 0.55 ± 0.32 logMAR to 0.46 ± 0.33 logMAR (p = 0.038). Mean CMT decreased from 473 ± 146 µm to 349 ± 85 µm (p < 0.001). Twelve eyes (24%) demonstrated absence of macular edema after aflibercept. Previous bevacizumab exposure did not correlate with different outcomes. The variation of VA in response to aflibercept was significantly superior in the group with poorer VA before the switch (mean variation of -0.097 ± 0.21 logMAR) when compared to eyes with VA < 0.4 logMAR (mean variation of +0.019 ± 0.090 logMAR; p = 0.036). The same scenario was verified for anatomical outcomes as eyes with poor vision before the switch (≥0.4 logMAR) achieved superior reduction in CMT in response to aflibercept (mean CMT variation of -157 ± 171 µm versus -49.5 ± 39.9 µm; p < 0.01). Pre-switch CMT was a predictor of CMT reduction after switching (B = -0.945; confidence interval 95% -1.1; -0.76; p < 0.001). CONCLUSIONS: Conversion to aflibercept for persistent DME resulted in functional and anatomical improvements and these outcomes were not influenced by previous bevacizumab exposure. Pre-switch CMT was a predictor of anatomical changes after aflibercept.

CHOROIDAL THICKNESS IN MULTISYSTEMIC AUTOIMMUNE DISEASES WITHOUT OPHTHALMOLOGIC MANIFESTATIONS.

PURPOSE: To evaluate choroidal morphology and thickness at the posterior pole of individuals affected by multisystemic autoimmune diseases and without known ophthalmologic manifestations. METHODS: Retrospective cross-sectional study including 75 patients with autoimmune diseases (divided according to their specific disease) and 80 healthy controls. A spectral-domain optical coherence tomography using enhanced depth imaging was performed and choroidal thickness was measured in the center of fovea and at 500 µm intervals along a horizontal section. RESULTS: Lupus patients presented a thicker subfoveal choroid than controls (408.624 vs. 356.536, P < 0.001) and in all the other measurements (P < 0.001 to P = 0.003). Rheumatoid arthritis and other autoimmune diseases had an overall thinner choroid than controls (297.867 vs. 356.536 subfoveally, P = 0.004; P = 0.005-0.019 in other measurements). Results were adjusted for the covariates age (P = 0.007), spherical equivalent (P < 0.001), and systemic steroids dose (P = 0.004). Hypertension (P = 0.102), diabetes mellitus (P = 0.672), time since the beginning of therapy with hydroxychloroquine (P = 0.104) and its cumulative dose (P = 0.307), or use of other immunosuppressives (P = 0.281) had no influence on the mean choroidal thickness. No morphologic abnormalities were found. CONCLUSION: The choroid may be subclinically involved in autoimmune diseases. However, the choroidal response seems to differ depending on the autoimmune disease. Infiltrative mechanisms specific for lupus may justify the thickened choroid found in these patients.

Long-Term Effect of Anti-VEGF Agents on Intraocular Pressure in Age-Related Macular Degeneration.

PURPOSE: To analyze the effect of anti-vascular endothelial growth factor (VEGF) agents on intraocular pressure (IOP) in patients with neovascular age-related macular degeneration (AMD). Materials andMethods: This is a retrospective study that included 72 patients treated unilaterally with anti-VEGF agents according to a pro re nata regimen. Fellow noninjected eyes (n = 72) were used as controls. IOP variation and the development of sustained ocular hypertension (OHT) were assessed both in the injected and in the fellow eyes. RESULTS: While the final IOP was not significantly different between the 2 groups, sustained OHT developed in 4.2% of the injected eyes and 1.4% of the controls. In the study group, no significant IOP variation was noted during follow-up in patients receiving ≤20 injections, but there was a significant increase in IOP with time in more frequently treated patients (p = 0.041). Comparison of both subgroups demonstrated that patients receiving >20 injections suffered significantly greater IOP variation (p = 0.034) during follow-up, and that these patients tended to require IOP-lowering treatment more frequently (p = 0.090). CONCLUSION: Multiple anti-VEGF injections lead to an increase in IOP, although this variation is not sufficient to cause development of OHT in the majority of patients.

The Portuguese Experience with Ocriplasmin in Clinical Practice.

AIM: Evaluate the real-life experience with ocriplasmin on vitreomacular traction (VMT) release and full-thickness macular hole (FTMH) closure in Portugal. METHODS: Multicentric, retrospective study of 83 eyes of 78 patients who were treated with intravitreal ocriplasmin for VMT with and without FTMH. Primary outcomes were VMT release and FTMH closure. Secondary outcomes included visual acuity changes and structural features on spectral-domain ocular coherence tomography. RESULTS: VMT resolved in 47 of the 83 eyes (56.6%) and 6 of the 12 FTMH were closed (50.0%). Mean best-corrected visual acuity (BCVA) improved from 65.1 at baseline to 70.8 ETDRS letters at the end of follow-up (p < 0.0001) with a mean follow-up of 138.8 days. Improvement in BCVA was significantly better in eyes with VMT release (p = 0.021). Approximately 73% of patients had normal ellipsoid zone integrity at the end of follow-up, 87% had no neurosensorial detachment and 40% had no intra- or subretinal fluid. CONCLUSION: VMT release and FTMH closure were achieved in more than half of the treated eyes and were correlated with significant BCVA improvements and favorable baseline characteristics. In fact, if a careful patient selection is carried out, VMT resolution with ocriplasmin can be optimized, tailoring the best approach to each patient.

Evaluation of visual acuity, macular status, and subfoveal choroidal thickness changes after cataract surgery in eyes with diabetic retinopathy.

PURPOSE: Progression of diabetic macular edema has been reported as a common cause of poor visual acuity recovery after cataract surgery in patients with diabetes. Despite being responsible for the blood supply to the outer retina, the role of the choroidal layer in the pathogenesis of diabetic retinopathy (DR) is not yet understood. Our objective is to characterize macular and subfoveal choroidal thickness changes after cataract surgery in eyes with DR. METHODS: Thirty-five eyes with clinically significant cataract of patients with DR were divided into three groups based on clinical and optical coherence tomography findings: patients with DR without macular edema, patients with DR and macular thickening detected on optical coherence tomography, and finally patients with clinically significant macular edema. All cases were submitted to ophthalmologic examination and spectral domain optical coherence tomography 1 week before cataract surgery and repeated 1 month after surgery. Patients with preoperative clinically significant macular edema were treated with intravitreal bevacizumab at the time of surgery. RESULTS: All groups showed a significant increase in visual acuity 1 month after surgery (P < 0.001). Mean foveal thickness increased significantly in all groups, including controls (P = 0.013), except in patients who were simultaneously treated with intravitreal bevacizumab (P = 0.933). An increase of maximum macular thickness of at least 11% was found in 25.7% of the DR eyes, but no such increase occurred in the control eyes. No significant change was verified for subfoveal choroidal thickness in any of the studied groups. CONCLUSION: Surgical inflammation associated with cataract surgery caused a significant increase of macular thickness in control and DR eyes that were not treated with intravitreous bevacizumab. Such macular changes were not accompanied by subfoveal choroidal thickness changes in any of the study groups, suggesting that the changes in macular thickness associated with the surgery are not related to changes in choroidal thickness and that there is no relation between inner blood-retinal barrier status and diabetic choroidal angiopathy.

INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR CHOROIDAL NEOVASCULARIZATION SECONDARY TO PATHOLOGIC MYOPIA: SIX YEARS OUTCOME.

PURPOSE: To report the visual outcome after 6-year follow-up in highly myopic eyes with choroidal neovascularization treated with anti-vascular endothelial growth factor drugs. METHODS: Retrospective, nonrandomized, multicenter, consecutive, and interventional case series. RESULTS: Seventy-eight patients were treated with intravitreal bevacizumab and 19 with ranibizumab. Mean age of the patients was 56.5 years (SD, 13.3). The average number of letters read was 56.7 (SD, 19.0) at baseline; 65.7 (SD, 18.4) at 12 months; 63.6 (SD, 20.6) at 24 months; 62.4 (SD, 21.4) at 36 months; 60.6 (SD, 22.0) at 48 months; 58.9 (SD, 22.9) at 60 months, and 58.4 (SD, 22.7) at 72 months (P < 0.01, between initial vs. 12, 24, and 36 months; P = 0.07, 0.3, and 0.5 between initial vs. 48, 60, and 72 months, respectively; Student's t-test paired data). The mean total number of intravitreal injections was 3.3 (SD, 2.3; range, 1-9). CONCLUSION: Bevacizumab and ranibizumab are effective therapies and show similar clinical effects in myopic eyes with choroidal neovascularization. Visual acuity gain is maintained at a 3-year follow-up. The improvement is no longer statistically significant at Years 4, 5, and 6.