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.

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 DEXAMETHASONE IMPLANT FOR RADIATION MACULOPATHY SECONDARY TO PLAQUE BRACHYTHERAPY IN CHOROIDAL MELANOMA.

PURPOSE: To evaluate the efficacy of intravitreal dexamethasone implant 0.7 mg (Ozurdex) in radiation maculopathy secondary to plaque brachytherapy in choroidal melanoma. METHODS: Twelve eyes diagnosed of radiation maculopathy secondary to plaque brachytherapy and treated with intravitreal dexamethasone implant were included. Visual acuity, foveal thickness using spectral domain optical coherence tomography, and grade of macular edema, using Horgan classification, were evaluated. RESULTS: Mean age was 65.5 ± 28 years (range, 40-82 years). Mean follow-up was 8.2 ± 7.8 months (range, 2-28 months). Mean visual acuity before treatment was, in logarithm of the minimum angle of resolution scale, 1 ± 0.58 (range, 0.4-2) and mean final visual acuity 0.8 ± 0.58 (range, 0.2-2), showing a nonsignificant trend to improvement (P = 0.091; Wilcoxon's test). Foveal thickness before treatment was 416 ± 263 µm (range, 222-725 µm) and final foveal thickness 254 ± 170 µm (range, 145-750), showing a significant decrease (P = 0.016; Wilcoxon's test). Referring to Horgan classification, a significant reduction in grades before and after treatment was demonstrated (P = 0.007; Wilcoxon's test). CONCLUSION: Ozurdex is a useful treatment for radiation maculopathy associated to plaque brachytherapy for uveal melanoma, with a significant decrease in foveal thickness and a significant improvement in Horgan classification. This anatomical improvement was correlated with a moderate improvement in visual acuity.

Subthreshold transpupillary thermotherapy in management of foveal subretinal fluid in small pigmented choroidal lesions.

PURPOSE: To evaluate the effect of subthreshold transpupillary thermotherapy (sTTT) in foveal subretinal fluid of small pigmented choroidal lesions. METHODS: Retrospective, noncomparative, interventional case series. We reviewed patients with small pigmented choroidal lesions presenting foveal subretinal fluid and treated with sTTT to evaluate fluid regression. RESULTS: We treated 13 patients with small pigmented choroidal lesions with a mean height of 2.02 ± 0.54 mm (range, 1.4-2.9 mm) and a mean largest diameter of 7.60 ± 1.98 mm (range, 5-11 mm). In 11 cases, foveal subretinal fluid was completely resolved (84.6%), with a mean follow-up of 42.46 ± 26.29 months (range, 12-103 months). The mean number of sTTT sessions applied was 1.38 ± 0.77 (range, 1-3 sessions), at a mean spot size of 1,570.59 ± 795.1 µm (range, 500-3,000 µm), and overall exposure time of 2.32 ± 1.2 minutes (range, 1-6 minutes). Mean laser power applied was 370.63 ± 162.87 mW (range, 200 to 600 mW). Best-corrected visual acuity at the time of diagnosis was maintained or improved in 69.3% of patients after sTTT treatment. During follow-up, tumor progression was reported in 5 cases, regardless of the presence of subretinal fluid. These cases were treated promptly with brachytherapy. CONCLUSION: However, sTTT may be effective in solving foveal subretinal fluid in small pigmented choroidal lesions, attaining satisfactory visual acuity in most cases.

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.

Orthotopic murine xenograft model of uveal melanoma with spontaneous liver metastasis.

Uveal melanoma is the most common intraocular malignancy in adults. Despite the effective primary treatment, up to 50% of patients with uveal melanoma will develop metastatic lesions mainly in the liver, which are resistant to conventional chemotherapy and lead to patient's death. To date, no orthotopic murine models of uveal melanoma which can develop spontaneous metastasis are available for preclinical studies. Here, we describe a spontaneous metastatic model of uveal melanoma based on the orthotopic injection of human uveal melanoma cells into the suprachoroidal space of immunodeficient NSG mice. All mice injected with bioluminescent OMM2.5 ( n = 23) or MP41 ( n = 19) cells developed a primary tumor. After eye enucleation, additional bioluminescence signals were detected in the lungs and in the liver. At necropsy, histopathological studies confirmed the presence of lung metastases in 100% of the mice. Liver metastases were assessed in 87 and in 100% of the mice that received OMM2.5 or MP41 cells, respectively. All tumors and metastatic lesions expressed melanoma markers and the signaling molecules insulin-like growth factor type I receptor and myristoylated alanine-rich C-kinase substrate, commonly activated in uveal melanoma. The novelty of this orthotopic mouse xenograft model is the development of spontaneous metastases in the liver from the primary site, reproducing the organoespecificity of metastasis observed in uveal melanoma patients. The faster growth and the high metastatic incidence may be attributed at least in part, to the severe immunodeficiency of NSG mice. This model may be useful for preclinical testing of targeted therapies with potential uveal melanoma antimetastatic activity and to study the mechanisms involved in liver metastasis.

Choriocapillaris and choroidal thickness in all Leber hereditary optic neuropathy stages using swept source technology.

PURPOSE: The role of the choroid in Leber hereditary optic neuropathy (LHON) remains unclear. The literature is scarce, with conflicting results and lacks axial length measurements. Therefore, we aimed to analyse the choriocapillaris (CC) vessel density (VD) and choroidal thickness (ChT) in all stages of LHON using swept source (SS) technology and considering the possible influence of axial length on choroidal parameters. METHODS: This was a prospective cross-sectional observational study. A total of 119 eyes of 60 patients with molecularly confirmed LHON across all stages and 120 eyes of 60 control participants were included. We obtained the CC VD using optical coherence tomography angiography maps centred on the fovea. ChT was measured from the Bruch's membrane to the choroid-sclera interface in the macular and peripapillary regions. RESULTS: The CC VD was not significantly affected in any sector or average, except for a slight change in the superior region of chronic eyes (52.08 ± 1.62% vs. 53.50 ± 2.29%, p = 0.002). ChT demonstrated a trend towards decreased values in asymptomatic eyes and increased values in the symptomatic stages that failed to reach statistical significance in sectors corresponding to the papillomacular bundle except for the macular nasal inner sector of chronic eyes (281.10 ± 67.12 µm vs. 252.08 ± 70.55 µm, p = 0.045). No significant correlations were observed between visual acuity and CC VD or ChT. CONCLUSION: The CC VD remained stable across the LHON stages. Choroidal vasculature does not appear to play a role in LHON pathophysiology. Further research is needed on ChT as a potential biomarker of LHON.

Quantitative assessment of macular and circumpapillary retinal vessel density across all stages of Leber hereditary optic neuropathy using swept source optical coherence tomography angiography.

PURPOSE: To investigate the macular and circumpapillary retinal microvasculature across all stages of Leber hereditary optic neuropathy (LHON) using swept source optical coherence tomography angiography (OCTA). METHODS: This prospective, multicentre, cross-sectional, observational study analysed a total of 119 eyes of 60 patients with molecularly confirmed LHON across all stages and 120 eyes of 60 control subjects. Optical coherence tomography angiography maps centred on the fovea and optic disc were obtained to measure vessel densities (VDs) in the macular superficial (SCP) and deep (DCP) capillary plexuses, and the radial peripapillary capillary plexus (RPCP) respectively. RESULTS: In asymptomatic eyes, only the SCP showed significant changes on average (B coefficient = -0.72, 95% CI = -1.34 to -0.10, p = 0.022) or in sectors representing the papillomacular bundle (PMB) (B coefficient = -1.17, 95% CI = -2.23 to -0.11, p = 0.031). However, in chronic eyes, the greatest magnitude of change was found in the temporal sector of the RPCP (B coefficient = -12.36, 95% CI = -14.49 to -10.23, p < 0.001). The RPCP showed the strongest correlations with visual acuity (VA, logarithm of the minimum angle of resolution; R = -0.677, p < 0.001) and structural parameters (R = 0.747, p < 0.001). CONCLUSIONS: Retinal VD changes in the circumpapillary region of the PMB appear later than in the macula but end up being more profound and correlate better with VA and structural parameters. Further studies are needed to assess the clinical utility of retinal VDs as potential LHON biomarkers.

Intravitreal infliximab in patients with macular degeneration who are nonresponders to antivascular endothelial growth factor therapy.

PURPOSE: The purpose of this study was to determine the efficacy and safety of intravitreal infliximab in the treatment of choroidal neovascularization secondary to age-related macular degeneration in patients who are nonresponders to antivascular endothelial growth factor therapy. METHODS: Prospective, noncomparative, interventional case series. The primary inclusion criteria for patients consisted of previous treatment with five or more intravitreal injections of bevacizumab and/or ranibizumab, visual loss, angiographic leakage, and intraretinal and/or subretinal fluid on spectral domain optical coherence tomography. At Day 0, a single intravitreal injection of infliximab (2 mg/0.05 mL) was administered. Best-corrected visual acuity testing measured with Early Treatment Diabetic Retinopathy Study charts and spectral domain optical coherence tomography scans were performed on Days 0, 3, 7, 30, 60, and 90. Fluorescein angiography was performed at days 0 and 90. The development of systemic antibodies against infliximab (human antichimeric antibodies) was not sought. Main outcome measures were changes in best-corrected visual acuity, foveal thickness, and lesion size. RESULTS: We included four patients. At Day 90, the best-corrected visual acuity change was -18, +3, +4, and -4 letters, respectively. Intraretinal and/or subretinal fluid on spectral domain optical coherence tomography scans was not significantly reduced in any case. Lesion size was not reduced in any case. Two patients developed intraocular inflammation with high intraocular pressure 3 and 5 weeks after the infliximab injection, respectively. One case was controlled with topical medication, and one case required posterior vitrectomy. CONCLUSION: Intravitreal infliximab showed no significant visual or anatomical benefit for the treatment of choroidal neovascularization secondary to age-related macular degeneration in patients who were nonresponders to antivascular endothelial growth factor therapy. In addition, half of the cases developed intraocular inflammation.

Prospective clinical trial evaluating the efficacy of photodynamic therapy for symptomatic circumscribed choroidal hemangioma.

PURPOSE: To evaluate photodynamic therapy (PDT) for symptomatic circumscribed choroidal hemangioma (CCH). DESIGN: Prospective, multicenter, nonrandomized clinical trial. PARTICIPANTS: Thirty-one eyes of 31 patients with posterior pole CCH and symptoms caused by exudation into the macular area. INTERVENTION: Photodynamic therapy was applied by Zeiss laser. Intravenous verteporfin at 6 mg/m(2) body surface was administered before treatment, and light emitted at 689 nm for photosensitization. The treatment spot diameter was calculated on early-phase frames of pretreatment indocyanine green angiography. Fifteen minutes after starting the verteporfin infusion, the laser beam was applied to the retina at radiant exposure 50 J/cm(2) and exposure time 83 seconds. One to 4 treatments were applied at 12-week intervals over 1 year. Standardized evaluation was performed before and at 4-week intervals after each treatment, and at 3, 6, 9, and 12 months. All patients were followed for >or=12 months. MAIN OUTCOME MEASURES: The primary outcome measure was the absence of exudative retinal detachment at the 12-month follow-up visit on ophthalmoscopy, fluorescein angiography, and optical coherence tomography. Secondary measures were the visual acuity outcome, with best-corrected visual acuity determined by the Early Treatment for Diabetic Retinopathy Study chart, tumor thickness decrease on B-scan ultrasonography, and adverse events. RESULTS: Among the total, 82.8% of patients required 1, 13.8% 2, and 3.4% 3 PDTs to eliminate exudative retinal detachment. Visual acuity increased from a mean of 20/60 to 20/35 (P<0.001). Sixty-nine percent of patients demonstrated visual recovery (P<0.001). Cystoid macular edema regressed in all cases and exudative macular detachment disappeared in all but 2 cases. The CCH thickness decreased in all cases from a mean of 3.0 to 1.7 mm, with the most intense effect seen after 4 weeks of treatment (P<0.001). Visual fields showed resolution of central scotomas. There were no severe adverse events. CONCLUSIONS: Combining PDT with the standard age-related macular degeneration protocol is an effective treatment for CCH in terms of resolution of exudative subretinal fluid and recovery of VA. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Uveal Melanoma: A European Network to Face the Many Challenges of a Rare Cancer.

Uveal melanoma (UM) is the most frequent primary ocular cancer in adults, accounting for 5% of all melanomas. Despite effective treatments for the primary tumour, up to 50% of UM patients will develop metastasis, leading to a very poor prognosis and a median overall survival of 6 to 12 months, with no major improvements in the last 30 years. There is no standard oncological treatment available for metastatic UM patients, and BRAF/MEK and immune checkpoint inhibitors show disappointing results when compared to cutaneous melanoma (CM). Recent advances in biology, however, identified specific gene and chromosome alterations, potentially permitting an actively tailored surveillance strategy, and dedicated clinical studies. Being a rare cancer, UM patients have to overcome issues such as identifying referral centres, having access to information, and partnering with oncologists for specific management strategies and research priorities. Here, we describe how the EUropean Rare Adult solid CAacer Network (EURACAN) will help in addressing these challenges and accelerating international collaborations to enhance the development of innovative treatments in UM.

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.

Two cases of accidental dislocation of the silicone sleeve of an extrusion cannula into the vitreous cavity.

BACKGROUND: Fluid-air exchange during vitreoretinal surgery is often used as a tool for subretinal fluid endodrainage. Soft-tipped flexible extrusion cannulas are commonly used to aspirate the posterior subretinal fluid. METHODS: This is an observational two-case series describing two patients who underwent 20-G pars plana vitrectomy complicated by the accidental fall of the silicone sleeve of a soft-tipped extrusion cannula into the vitreous cavity. In the first case, the cannula had inadvertently been subjected to sterilization process. RESULTS: While withdrawing the soft-tipped extrusion cannula from the eye, following internal drainage of transvitreal and subretinal fluid, the loose silicone sleeve probably got entangled at the inner lip of the sclerotomy and finally fell on the retinal surface. In both cases, the silicone sleeve was held and removed with an intraocular forceps. CONCLUSIONS: This rare complication has been reported in the literature only once previously. Sterilization of disposable subretinal fluid cannulas is not advisable because of the risk of dislocation of the silicone sleeve into the eye. Besides this, it is important to check the integrity of the silicone sleeve before and after surgery.

Acute onset of retinal detachment after posterior chamber phakic intraocular lens implantation.

CASE REPORT: A 34-year-old man with severe myopia, presented with acute visual loss in his right eye. This occurred 3 hours after a posterior chamber phakic (PCP) intraocular lens (IOL) implantation, and was associated with a rhegmatogenous retinal detachment. Retinal retachment surgery was performed without complications, with the outcome showing good anatomical and functional results during a 2-year follow-up period. DISCUSSION: Despite the fact that several authors have described retinal detachments following PCP IOL implantation in highly myopic patients, there is no evidence that this procedure increases the risk of retinal detachment in these patients. The occurrence of the retinal detachment immediately after the phakic IOL implantation supports the hypothesis that the surgical procedure could induce iatrogenic changes in patients with high myopia, which could increase the incidence of retinal detachment. In contrast to other reports, the interval between the PCP IOL implantation and the retinal detachment was only 3 hours in our patient. We believe this demonstrates the importance of performing a complete preoperative vitreoretinal examination in patients with severe myopia.