Changes in vessel density patterns assessed with OCTA in patients with diabetic macular edema treated with anti-VEGF therapy.

AIMS: To determine the presence of sectoral changes in vessel density (VD) patterns induced by vascular endothelial growth factor inhibitors (anti-VEGF) in patients with diabetic macular edema (DME) using optical coherence tomography angiography (OCTA). METHODS: Prospective, interventional study. A total of 43 patients (63 eyes) were initially enrolled in the study. We performed swept source (SS) OCT and sectorial OCTA measurement to determine parafoveal VD at baseline and after six months of anti-VEGF treatment. In the locations with statistically significant differences in VD between baseline and month 6, we performed univariate and multivariate analyses to determine which, if any, of the baseline variables were associated with the observed changes. RESULTS: A total of 34 patients (48 eyes) were included in the final analysis. Mean VD decreased from baseline to month 6 (from 45.2 (± 3.5) to 44.6 (± 3.2) % in the SCP and from 50 (± 3.3) to 49 (± 3.9) % in the DCP). The only significant changes in VD were observed in the nasal sector of the deep capillary plexus, with a decrease of 2.9% (p = 0.001). On univariate and multivariate analyses, the only variable significantly associated with changes in VD in the nasal sector after 6 months of treatment was baseline VD in the same sector. CONCLUSIONS: Anti-VEGF therapy has a small impact on VD values over time. These variations observed after treatment seems to be related to changes over areas of vascular anomalies and displaced vessels adjacent to cystic areas, with no significant changes over ischemic areas. No correlation was observed between this trend and other clinical baseline features.

Correlation between Topographic Vessel Density and Retinal Thickness Changes in Patients with Diabetic Macular Edema Treated with Anti-VEGF Therapy: Is It a Suitable OCTA Biomarker?

The objective of this study was to determine the correlation between topographic vessel density (VD) and retinal thickness (RT) reductions induced by vascular endothelial growth factor inhibitors (anti-VEGF) in patients with diabetic macular edema (DME) using optical coherence tomography angiography (OCTA). This was a prospective, interventional case series. VD and RT measurements were separately taken in four parafoveal subfields at baseline and after six months of treatment. This correlation was statistically assessed using Spearman's rho correlation coefficient after adjustment for multiple comparisons. The study included a total of 48 eyes in the final analysis. Mean VD decreased from baseline to month 6 (from 45.2 (±3.5) to 44.6% (±3.2) in the superficial capillary plexus and from 50 (±3.3) to 49% (±3.9) in the deep capillary plexus). Statistically significant reductions in RT were observed in all ETDRS sectors (p < 0.0001). No significant association was found between RT and VD, even when analyzing responders and non-responders separately. After six months of anti-VEGF treatment, no significant correlation was observed between the topographic VD and RT values. These findings suggest that reductions in VD values may not solely result from a reduction in microaneurysms, also being affected by the repositioning of displaced vessels due to edema and a reduction in their caliber. Therefore, VD changes may not be a suitable indirect OCTA biomarker of microaneurysm turnover and treatment response.

Local Resection in Choroidal Melanoma: A Review.

Surgical resection is widely used to treat small tumours located in the iris and the ciliary body, due to the accessibility of these sites. By contrast, surgical removal of choroidal tumours is substantially more challenging, which is why this procedure is performed only at specialised centres. In the present article, we review the literature on surgical resection of choroidal tumours, which can be performed as endoresection (ab interno) or transscleral resection (ab externo). An important aim of this review is to describe and compare the two approaches in terms of visual outcomes, survival rates, and complications. Both approaches are indicated for the removal of large tumours (thickness > 8 mm) with small base diameters. Surgical resection of the tumour allows clinicians to obtain valuable histopathologic and cytogenetic data from the specimen and eliminates the risks associated with radiotherapy. However, both of these surgical approaches are technically challenging procedures involving the risk of severe early and late postoperative complications.

Topical NSAIDs, intravitreal dexamethasone and peribulbar triamcinolone for pseudophakic macular edema.

BACKGROUND: The purpose of this study is to assess the effectiveness of topical nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids (intravitreal dexamethasone and peribulbar triamcinolone) in treating pseudophakic macular edema (PME). METHODS: Retrospective study of 33 eyes. Variables included best corrected visual acuity (BCVA; logMAR scale) and central retinal thickness (CRT) and central choroidal thickness (CCT) assessed with swept-source OCT. All patients were initially prescribed topical NSAIDs and reevaluated after 2 months. If improvement in BCVA or CRT was noted, topical NSAIDs were continued until resolution. If no improvement was observed at 2 months or subsequent visits, intravitreal dexamethasone implant was performed. Patients who refused intravitreal treatment were offered peribulbar triamcinolone. RESULTS: After treatment with topical NSAIDs for a median of 2 months, BCVA increased significantly from 0.5 to 0.3 while CRT decreased significantly from 435 to 316 µm. PME resolved in 19 of the 33 eyes (57.6%). Of the 14 recalcitrant cases, 13 were treated with corticosteroids. Of these 13 cases, 9 (69.2%) resolved. BCVA increased non-significantly from 0.7 to 0.4. CRT and CCT decreased significantly from 492 to 317 µm and from 204 to 182 µm respectively. CONCLUSIONS: The overall success rate of the treatment algorithm was greater than 80%, a remarkable finding considering that no randomized study has yet been conducted to determine the optimal therapeutic protocol for PME. This is the first study to evaluate choroidal thickness in PME using SS-OCT, which could play a key role in its pathophysiology and provide useful information to improve the management of PME.

Survival in small choroidal melanocytic lesions with risk factors managed by initial observation until detection of tumour growth.

BACKGROUND: The main objective was to describe metastatic and survival rates in patients with small choroidal melanocytic lesions initially managed by observation. METHODS: Retrospective, observational study of consecutive cases recruited from 2001 through 2018, followed for a median (mean, range) of 81.0 (89.3, 10-204) months in a tertiary referral centre for ocular oncology. Seventy-five consecutive patients diagnosed with small choroidal melanocytic lesions with risk factors for growth initially observed and who showed progression during follow-up. Treatment was performed (plaque radiotherapy or enucleation in 96% and 4% of cases, respectively) at detection of tumour growth. RESULTS: Median (mean, range) tumour thickness was 2.2 (2.23, 1.08-3.40) mm, and median maximum basal diameter was 8.5 (8.16, 4-12) mm. At diagnosis, a median (mean, range) of 5 (5.48, 1-8) risk factors for progression were present. Lesions grew at a median (mean, range) rate of 0.42 mm/y (1.12, 0-7.68) in thickness and 1.05 mm/y (3.14, 0-4.8) in maximum diameter. Median (mean, range) time until growth was 17.00 (32.6, 1-161) months post-diagnosis, at which time tumours were treated. Five patients developed local recurrence after brachytherapy requiring enucleation. Four patients developed hepatic metastasis. Melanoma-specific survival was 98% at 5 years (95% CI, 94.2-100%) and 91.6% (95% CI, 82-100%) at 10 and 15 years. CONCLUSION: In small melanocytic lesions with risk factors for growth, initial observation until detection of tumour growth results in a seemingly low risk of metastasis, suggesting that this may be an initial approach to consider in tumours with indeterminate malignant potential.

INTERNAL LIMITING MEMBRANE PEELING VERSUS NONPEELING TO PREVENT EPIRETINAL MEMBRANE DEVELOPMENT IN PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT: A Swept-Source Optical Coherence Tomography Study With a New Postoperative Classification System.

PURPOSE: To determine whether internal limiting membrane peeling in primary rhegmatogenous retinal detachment prevents epiretinal membrane (ERM) development. Secondarily, we propose a classification system for postoperative ERMs. METHODS: Retrospective, interventional, comparative case series. Consecutive eyes with primary rhegmatogenous retinal detachment (n = 140) treated by a single surgeon. The presence of postoperative ERMs was assessed with swept-source optical coherence tomography. RESULTS: An ERM was detected in 26 eyes (46.4%) in the nonpeeling group and in one eye (1.8%) in the internal limiting membrane peeling group (P ≤ 0.001). The median visual acuity significantly improved in both groups (P ≤ 0.001). Inner retinal dimples were observed in 41.1% of eyes in the internal limiting membrane peeling group versus 0% in the nonpeeling group (P ≤ 0.001), and they were not correlated with visual acuity (r = 0.011; P = 0.941). Based on swept-source optical coherence tomography findings, we identified three different types of ERMs: 7 (26.9%) were classified as Type 1, 12 (46.1%) as Type 2, and 7 (26.9%) as Type 3. Superficial retinal plexus deformations observed on optical coherence tomography angiography and en face images were detected in 100% of Type 3 ERMs, 41.6% of Type 2, and 0% of Type 1 (χ = 14.3; P = 0.001). Interestingly, all of the patients who presented these alterations also had metamorphopsia. CONCLUSION: Internal limiting membrane peeling in primary rhegmatogenous retinal detachment seems to prevent postoperative ERM development. Swept-source optical coherence tomography analysis is helpful to define and classify different types of ERMs and to establish the surgical indication for their removal.

Clinical predictors of survival in metastatic uveal melanoma.

PURPOSE: To determine the clinical factors that influence survival in patients with metastatic uveal melanoma. STUDY DESIGN: Single-center, retrospective review of patients' medical records. METHODS: The following data of ninety-nine consecutive patients (49 men, 50 women) with metastatic uveal melanoma were registered: patient demographics; primary tumor characteristics; features of first melanoma-related metastasis; symptoms and patient status at distant disease debut and metastasis treatment. Overall survival was analyzed by Kaplan-Meier estimates. A Cox proportional hazards regression model was applied to identify independent predictors associated with survival. RESULTS: Mean patient age at metastatic diagnosis was 60.7 years (standard deviation, 12.8). The liver was the first metastatic site in most (92.9%) cases. The median disease-free interval was 26 months (interquartile range, 34). Median overall survival after detection of the first metastasis was 8 months (interquartile range, 14). The baseline characteristics of the primary uveal melanoma were not associated with survival in patients with stage IV disease. In the multivariate analysis, the following factors at first metastatic diagnosis were associated with improved overall survival: disease-free interval > 36 months; better performance status; and normal serum lactate dehydrogenase and gamma glutamyl transpeptidase levels. Overall survival was not influenced by specific metastatic treatment. CONCLUSION: Although metastatic uveal melanoma has a poor prognosis, this study reveals the existence of several independent prognostic factors for prolonged overall survival. These findings may help improve survival estimates in patients with advanced disease.

Changes in Choroidal Thickness After Intravitreal Injection of Anti-Vascular Endothelial Growth Factor in Pachychoroid Neovasculopathy.

Purpose: We evaluate changes in choroidal thickness after intravitreal injection (IVI) therapy for pachychoroid neovasculopathy (PNV). Methods: An observational, retrospective, consecutive case series was studied of 18 patients (18 eyes) who underwent anti-vascular endothelial growth factor (VEGF) therapy for PNV. The 18 fellow eyes in these patients were used as controls. All eyes were evaluated with swept-source optical coherence tomography (SS-OCT) and optical coherence tomography angiography (OCTA). Results: Mean patient age was 68.3 ± 7.0 years. Mean follow-up was 16.4 ± 2.0 months. No differences in the best-corrected visual acuity (BCVA) of the affected eyes were observed between baseline and 12-month follow-up (median Early Treatment of Diabetic Retinopathy Study [ETDRS] score, 77.5 vs. 76 letters, P = 0.074; median logMAR, 0.22 vs. 0.22, P = 0.453). However, subfoveal choroidal thickness (SFCT) decreased significantly from a mean of 317.7 ± 39.9 µm at baseline to 266.9 ± 56.3 µm at 12 months (P ≤ 0.001). Median change in SFCT at 12 months was 44.0 µm (range, 17-133 µm). SFCT decreased by 16% from baseline to month 12. The change in SFCT at 12 months was highly correlated with the number of IVI (rs = 0.762, P ≤ 0.001). No significant changes in SFCT were observed in the fellow eyes over the 12-month study period (median, 267.5 vs. 267.0 µm; P = 0.930). Conclusions: Choroidal thickness decreased significantly from baseline to month 12 in eyes with PNV treated with anti-VEGF injections. This reduction might be attributable to a reduction in choroidal vascular permeability and, thus, with a decrease in PNV activity. Prospective studies are needed to confirm these findings.

Prognostic Factors and Decision Tree for Long-Term Survival in Metastatic Uveal Melanoma.

PURPOSE: The purpose of this study was to demonstrate the existence of a bimodal survival pattern in metastatic uveal melanoma. Secondary aims were to identify the characteristics and prognostic factors associated with long-term survival and to develop a clinical decision tree. MATERIALS AND METHODS: The medical records of 99 metastatic uveal melanoma patients were retrospectively reviewed. Patients were classified as either short (≤ 12 months) or long-term survivors (> 12 months) based on a graphical interpretation of the survival curve after diagnosis of the first metastatic lesion. Ophthalmic and oncological characteristicswere assessed in both groups. RESULTS: Of the 99 patients, 62 (62.6%) were classified as short-term survivors, and 37 (37.4%) as long-term survivors. The multivariate analysis identified the following predictors of long-term survival: age ≤ 65 years (p=0.012) and unaltered serum lactate dehydrogenase levels (p=0.018); additionally, the size (smaller vs. larger) of the largest liver metastasis showed a trend towards significance (p=0.063). Based on the variables significantly associated with long-term survival, we developed a decision tree to facilitate clinical decision-making. CONCLUSION: The findings of this study demonstrate the existence of a bimodal survival pattern in patients with metastatic uveal melanoma. The presence of certain clinical characteristics at diagnosis of distant disease is associated with long-term survival. A decision tree was developed to facilitate clinical decision-making and to counsel patients about the expected course of disease.

Feasibility of swept-source OCT for active birdshot chorioretinopathy.

PURPOSE: To assess the feasibility of swept-source optical coherence tomography (SS-OCT) for clinical follow-up of patients with birdshot chorioretinopathy (BC). METHODS: Prospective longitudinal, observational, 12-month case-control study in a tertiary care center. The study population included 12 patients (24 eyes) diagnosed with BC and 21 age- and sex-matched healthy controls (42 eyes). The macular areas in both affected and healthy eyes were prospectively analyzed with SS-OCT at 1050 nm, using 2D 12.0-mm radial and horizontal scans and the 3D raster scan protocol (12.0 × 9.0 mm). Anatomical and structural abnormalities, as well as retinal and choroidal thickness (measured automatically), were evaluated and compared with visual field (VF) testing and indocyanine green angiography (ICGA). RESULTS: The most common qualitative abnormalities in the retina were thinning/loss of architecture and outer retinal hyperreflective foci, and in the choroid they were focal depigmentation, thinning/absence of Sattler's layer, generalized thinning, and hyperreflective foci. The most significant changes in the retina from baseline to the 12-month follow-up were decreases in intraretinal cysts, subretinal fluid, and hyaloid thickening. In the choroid, focal depigmentation decreased significantly, while vascular pattern loss increased. Compared to the healthy volunteers, patients with BC had thinner choroids and retinas at both baseline and study end. Retinal thickness decreased significantly in BC patients over the 12-month study period, but choroidal thickness remained unchanged. Findings from ICGA, VF, and SS-OCT were perfectly correlated in most (≈ 60%) patients. CONCLUSIONS: SS-OCT is a non-invasive, rapid method of assessing choroidal and retinal changes in patients with birdshot disease. This technique provides a simple method of monitoring the course of the disease that can be used to complement conventional tests.

DOME-SHAPED MACULA IN MYOPIC EYES: Twelve-Month Follow-up.

PURPOSE: To study the long-term clinical course of dome-shaped macula in myopic eyes and to evaluate treatment efficacy for subretinal fluid (SRF) as a related complication. METHODS: A retrospective, single-center consecutive case series study was conducted. The authors analyzed myopic eyes with dome-shaped macula in patients who presented for evaluation of decreased vision. Dome-shaped macula was defined as a convexity of the retina-choroidal macular complex seen on spectral domain optical coherence tomography images. All patients were followed for at least 12 months (mean, 25 months). Fluorescein angiography and/or indocyanine green angiography were performed in cases with SRF to rule out choroidal neovascularization. RESULTS: A total of 56 dome-shaped macula eyes from 36 patients were included in the study (bilateral in 55% of patients). Mean patient age was 56.9 ± 13.1 years. The mean spherical equivalent was -9.1 ± 6.0 diopters; 53% of eyes were considered highly myopic (>-6 diopters) and 47% of eyes were mildly myopic. In most cases (37 eyes; 66.1%), the dome-shaped macula was detected on vertical spectral domain optical coherence tomography scan patterns. No significant changes (P ≥ 0.1) were observed in mean best-corrected visual acuity or mean central foveal thickness from baseline to final follow-up. Subretinal fluid was present in 29 eyes (51.8%) at baseline, with no differences in best-corrected visual acuity in eyes with and without SRF (P ≥ 0.05). Nineteen of the 29 SRF eyes were treated: 8 underwent low-fluence photodynamic therapy, whereas 7 received bevacizumab, and 4 ranibizumab. No significant differences were found between treated and untreated SRF eyes in best-corrected visual acuity improvement (P ≥ 0.1), or complete resolution of SRF (P ≥ 0.1). Likewise, photodynamic therapy did not yield any significant benefit versus untreated eyes in best-corrected visual acuity or improvement of SRF. CONCLUSION: Dome-shaped macula is a condition associated with myopic eyes that seems to remain stable over time in terms of vision and macular profiles. It is often associated with chronic SRF, for which no effective treatment is current available. However, SRF does not seem to be a significant cause of visual impairment.

Tumor Volumes in Choroidal Melanoma: Agreement Between Three-Dimensional Ultrasound and Two Mathematical Models.

PURPOSE: To determine the degree of agreement between 2 mathematical models and 3-dimensional ultrasonography (3DUS) in estimating choroidal melanoma tumor volumes. DESIGN: Reliability analysis. METHODS: Tumor measurements estimated by 2 mathematical models (designated Formula 1 and Formula 2) were compared to those obtained by 3DUS in 45 consecutive patients with primary choroidal melanoma to determine the percentage agreement between the models and 3DUS. RESULTS: Both formulas tended to overestimate the tumor volume. Overall, the mean volume differences between 3DUS and Formula 1 and between 3DUS and Formula 2, respectively, were 51.7 mm(3) (95% confidence interval [CI], 187.6 to 84.3) and 23.8 mm(3) (95% CI, 122.5 to 74.8). Excluding mushroom-shaped tumors, the mean volume differences were 52.0 mm(3) (95% CI, 194.9 to 91.0) and 23.0 mm(3) (95% CI, 127.0 to 81.0), respectively. In mushroom-shaped tumors, mean volume differences were 49.9 mm(3) (95% CI, 135.7 to 35.9) and 29.3 mm(3) (95% CI, 87.6 to 29.0), respectively. CONCLUSIONS: The agreement between these mathematical models and the measured 3DUS volume was high. The data obtained in this study show that both formulas provide a simple, fast, and accurate method of estimating tumor volumes in the clinical setting, suggesting that these models could be used as a reliable and inexpensive alternative to time-consuming procedures such as 3DUS or magnetic resonance imaging. The accurate tumor volume values provided by these formulas may help to provide more reliable estimates of tumor regression or regrowth following globe-preserving treatment of choroidal melanomas, and may be a valuable prognostic indicator.

INCIDENCE AND RELATION WITH ANATOMICAL AND FUNCTIONAL VARIABLES OF POSTOPERATIVE MACULAR DISPLACEMENT IN RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To investigate the incidence of postsurgical retinal displacement in patients treated with pars plana vitrectomy for rhegmatogenous retinal detachment and to assess the influence of displacement on macular function. METHODS: Observational prospective study of 20 consecutive cases of rhegmatogenous retinal detachment who underwent 23-G pars plana vitrectomy with gas (C3F8 or SF6) tamponade, and prone resting. Three months after surgery, retinal displacement was evaluated by fundus autofluorescence. Macular function was evaluated with optical coherence tomography, multifocal electroretinogram, best-corrected visual acuity, and stereopsis. RESULTS: Postoperative retinal displacement was observed in 60% of cases. No correlation between the type of tamponade used and retinal displacement was observed. Similarly, no association between retinal displacement and postoperative stereopsis or visual acuity was found. A lower amplitude in P1 wave on the multifocal electroretinogram was observed in eyes with rhegmatogenous retinal detachment compared with the contralateral eye. However, no statistically significant differences between groups with or without retinal displacement were found. CONCLUSION: Retinal displacement in patients who undergo pars plana vitrectomy to treat rhegmatogenous retinal detachment is common. However, this displacement does not seem to affect macular function.

Autofluorescence and axial length as prognostic factors for outcomes of macular hole retinal detachment surgery in high myopia.

PURPOSE: To evaluate the results of fundus autofluorescence and axial length as prognostic factors for surgical outcome of macular hole retinal detachment in high myopic patients. METHODS: This is a retrospective, interventional, nonrandomized study. Patients were treated with posterior vitrectomy, internal limiting membrane peeling, and silicone oil tamponade. Best-corrected visual acuity, axial length, fundus autofluorescence, and spectral domain optical coherence tomography images were obtained. RESULTS: Fifteen eyes from 15 patients (mean age, 69.4 years) were evaluated. The mean refractive error was -19 diopters, and the mean axial length was 29.9 mm. The mean best-corrected visual acuity (logMAR) improved from 2.17 to 1.42 (P = 0.02) after a mean follow-up of 19.3 months. Spectral domain optical coherence tomography scans showed retinal detachment resolution in 13 eyes (86.6%) and macular hole closure in 9 eyes (60%). Fundus autofluorescence showed macular hypoautofluorescence with foveal involvement (mean area of 9.7 mm2) in 10 eyes (66.6%). Postoperative best-corrected visual acuity was significantly worse in these eyes (P = 0.009). Axial length >30 mm was found in the 2 cases with recurrent retinal detachment and in 4 of the 6 cases without macular hole closure (66.6%). CONCLUSION: Macular hole retinal detachment in high myopic patients can be successfully treated with vitrectomy, internal limiting membrane peeling, and silicone oil. Axial length >30 mm and macular hypoautofluorescence with foveal involvement seem to be prognostic factors for a worse anatomical and visual outcome.

Intravitreal ranibizumab for choroidal neovascularization secondary to pathological myopia: 12-month follow-up.

PURPOSE: To evaluate the efficacy and safety of intravitreal ranibizumab in the treatment of choroidal neovascularization (CNV) due to pathological myopia (PM). METHODS: This retrospective case series studied outcomes in patients with CNV secondary to PM who were treated with intravitreal ranibizumab. Patients underwent complete ophthalmic evaluation, which included best-corrected visual acuity testing measured with Early Treatment Diabetic Retinopathy Study charts, optical coherence tomography (OCT) and baseline fluorescein angiography (FA). Indications for retreatment included the persistence of subretinal fluid on OCT as well as hemorrhages and new CNV on FA. Patients were followed for a minimum of 12 months. RESULTS: We treated 29 eyes in 29 patients; the mean age was 56.8 years. Thirteen eyes were naïve, while 16 had been previously treated with photodynamic therapy or intravitreal bevacizumab. The mean initial visual acuity was 44.8 letters; at the 12-month follow-up, it was 53.7 letters. The mean OCT foveal thickness decreased by 35.3 µm. Patients received an average of 1.38 injections. Statistically significant differences were observed both in visual acuity and in central foveal thickness. All subgroups had favorable outcomes. None of the patients developed injection-induced complications or drug-related side effects. CONCLUSION: Intravitreal injection of ranibizumab appears to be safe and efficacious in patients with CNV secondary to PM followed over a 12-month period.