New insights in pathogenic mechanism of hydroxychloroquine retinal toxicity through optical coherence tomography angiography analysis.

INTRODUCTION: There is only a unique report with a small sample size studying hydroxychloroquine (HCQ) retinal toxicity with swept-source (SS) optical coherence tomography angiography (OCTA). The aim of this study was to quantify OCTA quantitative parameters in patients who underwent HCQ therapy. METHODS: We conducted a retrospective study. The study included 43 eyes of 22 patients taking HCQ for more than 5 years (high-risk group), 57 eyes of 29 patients taking HCQ for 5 years or less (low-risk group) and 25 eyes of 50 age-matched healthy controls. OCTA quantitative parameters (vessel density (VD) and foveal avascular zone (FAZ) area in superficial capillary plexus (SCP), middle capillary plexus (MCP), deep capillary plexus (DCP), total capillary plexus (TCP), and choriocapillaris (CC)) were recorded. RESULTS: In the low-risk group, VD in the SCP and MCP was increased compared to control group (p value <.05). In the high-risk group, VD in the SCP, MCP and TCP was increased (p value <.05). The subgroup analysis revealed an increased VD at SCP in systemic lupus erythematosus (SLE) high-risk patients, an increased VD at TCP and CC in rheumatoid arthritis (RA) high-risk subjects, and a decreased VD at CC level in the high-risk group patients with Sjögren's syndrome (SS) and connective tissue disease (CTD) (p value <.05). Furthermore, we demonstrated a significant enlargement of FAZ area at MCP level in the high-risk group patients with SS and CTD (p value <.05). CONCLUSION: We demonstrated an increase of VD in patients who underwent HCQ treatment, so we suggest that HCQ retinal toxicity is not vascular mediated.

Case Report: Ipilimumab-induced Multisystem Autoimmune-like Toxicities Suggestive of Vogt-Koyanagi-Harada-like Syndrome.

SIGNIFICANCE: The emergence of new cancer therapies has dramatically improved outcomes in metastatic melanoma. Immune checkpoint inhibitors have been the most effective treatment. Although, as a direct consequence of the immune dysregulation induced by them, adverse effects termed immune-related adverse events are observed in more than 60% of the patients. PURPOSE: We describe the clinical presentation of Vogt-Koyanagi-Harada-like syndrome in a patient with concomitant systemic melanoma treatment with ipilimumab, a cytotoxic T lymphocyte-associated antigen 4 blocker. METHODS: This study aimed to report a case of ipilimumab-induced vitritis, papillitis, and skin and auditory signs suggestive of Vogt-Koyanagi-Harada-like syndrome. CASE REPORT: A 64-year-old woman with metastatic melanoma presented with bilateral blurred vision and hearing loss upon completion of three cycles of treatment with ipilimumab. Ophthalmologic examination revealed a bilateral granulomatous uveitis with intense vitritis and papillitis. The result of optical coherence tomography was normal, and fluorescein angiography confirmed the bilateral papillary edema. Ipilimumab was withdrawn, and treatment with oral and systemic steroids led to a rapid improvement in the ophthalmologic and auditory manifestations. Three months after initial presentation, the patient developed vitiligo and poliosis. CONCLUSIONS: Vogt-Koyanagi-Harada-like syndrome can develop in the process of immunological deregulation by ipilimumab in the treatment of metastatic melanoma and can correlate temporally with the efficacy of the drug in tumor regression. These observations may help elucidate the underlying mechanism of Vogt-Koyanagi-Harada syndrome as well as the relation between tumor-associated tolerance and autoimmunity.

Rituximab in the treatment of Susac's syndrome: Report of a case.

SIGNIFICANCE: Susac's syndrome is a rare retinocochleocerebral immune-mediated endotheliopathy and clinically manifests as a pathognomonic triad of encephalopathy, hearing loss, and branch retinal artery occlusion. This triad is rarely present at symptom onset, thus, it is often initially misdiagnosed. To date, Susac's syndrome has persisted as an elusive entity and there are numerous treatment regimens proposed with varying effectiveness mainly based on case series. PURPOSE: To report our 12-month follow-up experience in the treatment of Susac's syndrome with rituximab. CASE REPORT: A 25-year-old female presenting with headache, paresthesias, tinnitus, peripheral vertigo, and a branch retinal artery occlusion. The patient had a personal history of anxiety-depressive disorder. After discarding other infectious/autoimmune conditions and magnetic resonance imaging suggestive findings of Susac's syndrome, we observed a prompt response to the combination of intravenous immunoglobulin, corticosteroids, and rituximab. CONCLUSION: A standard treatment paradigm is lacking in Susac's syndrome as randomized controlled trials do not exist. There are no definitive scores to predict its outcome, and early diagnosis is important as the organs involved can easily become irreversibly damaged. Thus, patients with Susac's syndrome must be treated promptly and aggressively. Our report highlights the possibility of positive long-term prognosis with an early use of rituximab. However, a systematic therapeutic approach on the basis of controlled trials is mandatory to develop a consensus.

The first case of fungal endogenous endophthalmitis caused by Aspergillus nidulans: Diagnostic and therapeutic challenge.

SIGNIFICANCE: Fungal endogenous endophthalmitis is an uncommon and potentially blinding infection. Aspergillus is a causative organism in immunocompromized although is virulent enough to afflict immunocompetents. Their propensity to affect macula usually results in a dismal prognosis; thus, improving visual outcome has always been challenging to clinicians. A. nidulans has only rarely been implicated in exogenous endophthalmitis. PURPOSE: To report the first case of A. nidulans endogenous endophthalmitis. CASE REPORT: An asthmatic 42-year-old female presented with sudden unilateral vision loss due to a submacular abscess that progressively worsened in a matter of days. Vitreous PCR analysis after an urgent vitrectomy was positive for A. nidulans with no active systemic foci found. Oral and intravitreal Voriconazole was prescribed but multiple reactivations led to three vitrectomies in total alongside with subretinal Voriconazole, abscess aspiration, and endolaser. There was complete resolution of the infection and, although visual acuity was poor due to macular scar, enucleation was avoided. CONCLUSION: Although uncommon, we must consider Aspergillus as the causative organism in apparently immunocompetent patients with history of recent systemic corticosteroids treatment, especially if they suffer a broncopulmonary disorder. Aspergillus is an aggressive organism so a high index of suspicion along with early diagnosis and prompt treatment is the key for better outcomes. We highlight A. nidulans as the causative agent as there are no other reported cases.

CRMP-5-IgG Antibody: role in the bilateral uveitis with swollen disc.

Autoimmunity against collapsin response-mediator protein-5 (anti-CRMP-5) has been associated with ocular inflammation in paraneoplastic syndrome. We present a 59-year-old Caucasian man with optic neuritis and vitreous cells in both eyes (OU), at different stages. Despite the fact that the patient did not have any systemic disease, we suspected a paraneoplastic syndrome and requested CRMP-5-IgG and a mediastinoscopy. After performing the tests, a small cell lung carcinoma was diagnosed. Autoantibody CRMP-5-IgG positivity and optic neuritis combined with vitreous inflammation was defined as a paraneoplastic entity, avoiding vitreous biopsy and allowing us to suspect malignancy before systemic symptoms appeared.

Analysis of anatomical biomarkers in subtypes of diabetic macular edema refractory to anti-vascular endothelial growth factor treated with dexamethasone implant.

INTRODUCTION: To analyze functional and anatomical outcomes in subtypes of diabetic macular edema treated with a single dexamethasone implant and to assess the usefulness of a pro-re-nata treatment among subtypes. METHODS: Retrospective study in morphologic patterns of diabetic macular edema (diffuse retinal thickening n = 15; cystoid macular edema n = 38, and serous retinal detachment n = 17) recalcitrant to anti-vascular endothelial growth factor, treated with dexamethasone implant. Examinations included timing to recidive of diabetic macular edema, best-corrected visual acuity, and central subfield macular thickness at 2, 4, and 6 months. RESULTS: In previously treated patients with a mean of 6.64 ± 3.69 anti-vascular endothelial growth factor injections, the best-corrected visual acuity improved from 61.64 ± 13.71 to 65.71 ± 14.65 as per the Early Treatment Diabetic Retinopathy Study protocol (p = 0.009) and central subfield macular thickness change from 447.46 ± 110.82 to 354.39 ± 80.46 µm (p < 0.005). The best-corrected visual acuity improvement was better in the diffuse retinal thickening group (68.67 ± 13.81 vs 65.26 ± 14.04 in cystoid macular edema and vs 64.12 ± 17.06 in serous retinal detachment), whereas higher central subfield macular thickness thinning was observed in serous retinal detachment group (368.47 ± 29.96 to 310.27 ± 67.47 in diffuse retinal thickening, vs 445.92 ± 105.06 to 364.39 ± 80.28 and 520.59 ± 122.96 to 370.94 ± 81.73 in cystoid macular edema and serous retinal detachment, respectively). Cystoid macular edema group was the group with more recurrences after 6 months (86.8% vs 66.7% in diffuse retinal thickening and 70.6% in serous retinal detachment). CONCLUSION: Dexamethasone implant is effective for all persistent diabetic macular edema subtypes with sustained functional and morphologic gains in the first 6 months.

Intravitreal dexamethasone implant Ozurdex® in naïve and refractory patients with different subtypes of diabetic macular edema.

BACKGROUND: Diabetic macular edema (DME) can be treated with different alternatives, among them Dexamethasone intravitreal implant 0.7 mg (DEX 0.7) has demonstrated that may improve both central macular thickness (CMT) and best corrected visual acuity (BCVA). This study aimed to evaluate the effect of the intravitreal dexamethasone implant Ozurdex® in patients with different subtypes of diabetic macular edema over a 6-month follow-up period. METHODS: Eighty-four (29 naïve and 55 previously treated) eyes were included in this retrospective study. For each patient, the BCVA [Early Treatment Diabetic Retinopathy Study (ETDRS) charts] and macular thickness on optical coherence tomography (OCT) at baseline visit and within the 2nd, 4th, and 6th months of follow-up were obtained. The main outcomes measurements were the mean change in BCVA and in CMT with respect to the baseline value. The percentage of patients gaining ≥5 letters and ≥ 10 letters in BCVA was also analyzed. RESULTS: A total of 84 eyes, 29 (34.5%) naïve and 55 (65.5%) non-naïve, from 69 patients were included in the study. BCVA at baseline was 58.8 (16.4) and 61.8 (11.6) in naïve and refractory patients, respectively, p = 0.4513. At every visit, BCVA significantly improved from baseline in naïve and non-naïve eyes (p < 0.0001 and p = 0.0003, respectively; Friedman rank sum test). At baseline, the mean CMT was 466.2 (189.7) µm and 448.1 (110.7) µm in the naïve and non-naïve patients, respectively (p = 0.5830); and decreased to 339.3 (92.5) µm and 357.5 (79.1) µm, respectively (p = 0.0004 and p < 0.0001, respectively, Wilcoxon signed-rank test). The proportion of patients gaining ≥10 letters was significantly greater in the naïve group, p = 0.0199. CONCLUSION: The intravitreal dexamethasone implant (Ozurdex) is effective for the treatment of diabetic macular edema, even in refractory cases that have failed to respond to previous therapies.

Sequential Dexamethasone and Aflibercept Treatment in Patients with Diabetic Macular Edema: Structural and Functional Outcomes at 52 Weeks.

OBJECTIVE: The aim of this paper is to compare intravitreous aflibercept versus dexamethasone implant followed by aflibercept (sequential treatment group) in patients with diabetic macular edema (DME). METHODS: We conducted an observational retrospective study in naïve DME patients, 15 treated only with aflibercept (a monthly injection for the first 5 consecutive doses, followed by an injection every 2 months), and 15 treated with a single dexamethasone implant followed by bimonthly aflibercept. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and qualitative features as well as adverse events were assessed at baseline and at 2, 6, and 12 months. RESULTS: BCVA increased from 70.8 ± 4.1 to 83.5 ± 2.7 letters with aflibercept and from 75.6 ± 2.7 to 86.5 ± 2.5 with sequential treatment (p = 0.551). CMT decreased from 411 ± 26.1 to 288.1 ± 10.5 with aflibercept and from 411.4 ± 24.3 to 260.8 ± 17.9 in the sequential treatment group. The differences between the 2 groups, in terms of visual gain and decreased MT, were not statistically significant (p > 0.05). Nine and 6 injections and 9 and 7 monitoring visits were performed. CONCLUSION: Sequential treatment in DME, starting with dexamethasone and followed by aflibercept, is a promising alternative that can reduce the treatment burden in the first year without statistically significant differences in terms of visual gain and decreased MT compared to aflibercept only.