Efficacy and safety of brolucizumab for serous drusenoid pigment epithelium detachment non-responder to bevacizumab and aflibercept.

INTRODUCTION: We report the case of a woman with drusenoid pigment epithelial detachment (DPED) in age-related macular degeneration who was successfully treated with two monthly intravitreal injections of brolucizumab after failing to respond to previous intravitreal injections of bevacizumab and aflibercept. CASE DESCRIPTION: A 56-year-old woman with mixed DPED and overlying subretinal fluid in her right eye was initially treated with three intravitreal injections of bevacizumab and three intravitreal injections of aflibercept with no visual and anatomical improvement. Switching to intravitreal injection of brolucizumab was performed. After two consecutive monthly intravitreal injections of brolucizumab, optical coherence tomography (OCT) showed first subretinal fluid resolution and then DPED collapse in the following months. After nine months, the best corrected visual acuity had improved from 20/40 to 20/20. There were no signs of retinal atrophy and exudative activity on OCT examination. No serious or minor adverse events were reported during the follow-up period. CONCLUSIONS: Switching to intravitreal brolucizumab injection might be an effective therapeutic option for treatment of mixed DPED with subretinal fluid refractory to other anti-VEGF drugs.

PERIPAPILLARY RETINAL NERVE FIBER THICKNESS CHANGES AFTER VITRECTOMY FOR EPIRETINAL MEMBRANE IN EYES WITH AND WITHOUT VITREOUS DETACHMENT.

PURPOSE: To compare the changes in postoperative peripapillary retinal nerve fiber layer (p-RNFL) thickness after vitrectomy for epiretinal membrane in eyes with preexisting posterior vitreous detachment (PVD) and eyes with surgically induced PVD. METHODS: This study included consecutive patients who underwent 25-gauge vitrectomy for epiretinal membrane. Eyes were divided, according to intraoperative PVD status, into a preexisting PVD group and surgically induced PVD group. Best-corrected visual acuity, p-RNFL thickness, and central retinal thickness were performed before and at 1, 3, and 6 months after surgery. RESULTS: One hundred and twenty eyes of 120 patients were enrolled: 64 eyes in the preexisting PVD group and 56 eyes in the surgically induced PVD group. In the preexisting PVD group at 6 months, the mean global p-RNFL thickness did not change, whereas it was reduced in the temporal sector (P = 0.034). In the surgically induced PVD group at 6 months, significant decreases were observed in global p-RNFL thickness (P = 0.027), temporal (P = 0.021), temporal inferior (P = 0.030), and nasal inferior sectors (P = 0.010). At 6 months, the two groups differed significantly in temporal (P < 0.001) and temporal inferior sectors (P = 0.004). The preoperative mean best-corrected visual acuity improved significantly at 6 months in both groups. CONCLUSION: Postoperative p-RNFL thickness after vitrectomy for epiretinal membrane tended to decrease in the temporal sector in all eyes and in the temporal inferior and nasal inferior sectors in eyes with surgically induced PVD.

EN FACE OPTICAL COHERENCE TOMOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF MULTIPLE EVANESCENT WHITE DOT SYNDROME: New Insights Into Pathogenesis.

PURPOSE: To localize the various levels of abnormalities in multiple evanescent white dot syndrome by comparing "en face" optical coherence tomography (OCT) and OCT angiography with various conventional imaging modalities. METHODS: In this retrospective case series, multimodal imaging was performed in 9 retinal centers on 36 patients with multiple evanescent white dot syndrome and included widefield fundus autofluorescence (FAF), fluorescein angiography (FA), and indocyanine green angiography, and B-scan and "en face" C-scan enhanced depth imaging and spectral domain OCT. Optical coherence tomography angiography was also performed at the level of the superficial and deep retinal capillary plexus and choroid. RESULTS: Multiple evanescent white dot syndrome lesions were more numerous and more easily detectable with FA and FAF. Two types of lesions were identified with FAF, FA, and indocyanine green angiography: larger widely scattered "spots" (approximately 200 µ in diameter) that were hyperfluorescent with FA, hyperautofluorescent with FAF, and hyporeflective in indocyanine green angiography, representing abnormalities primarily at the retinal pigment epithelium/photoreceptor junction; and punctate "dots" (less than 100 µ in diameter) that were hyperfluorescent with FA, hyperautofluorescent, or isoautofluorescent with FAF, and hypofluorescent with indocyanine green angiography and that localized to the outer nuclear layer. These lesions colocalized with "en face" OCT. The larger confluent "spots" were hyporeflective and colocalized to the level of the ellipsoid zone, whereas smaller hyperreflective "dots" colocalized to the outer nuclear layer. The location of the "dots" in the outer nuclear layer was further confirmed by structural spectral domain optical coherence tomography which showed coalescence of the dots into hyperreflective lines extending from the external limiting membrane to the outer plexiform layer in certain cases. Optical coherence tomography angiography analysis of the retinal microvasculature and choriocapillaris and choroid were entirely unremarkable in 100% of our patients. CONCLUSION: By combining multimodal imaging, the authors propose that multiple evanescent white dot syndrome is primarily the result of inflammation at the outer photoreceptor level leading to a "photoreceptoritis" and causing loss of the inner and outer segments. Its evanescent nature suggests that the photoreceptor cell bodies remain intact ensuring complete recovery of the photoreceptor inner and outer segments in most cases, compatible with the clinical course of spontaneous resolution of white spots and dots.

Demyelinizing Neurological Disease after Treatment with Tumor Necrosis Factor-α Antagonists.

PURPOSE: Demyelinizing neurological disease is a rare complication after treatment with tumor necrosis factor (TNF)α antagonists. We report on a case of multiple sclerosis after TNFα antagonist treatment and discuss its differential diagnosis. METHODS: This is an observational case study. RESULTS: A 48-year-old male was referred to Ophthalmology in January 2015 for an absolute scotoma in the superior quadrant of the visual field in his right eye. Visual acuity was 20/50 in the right eye and 20/20 in the left. Fundus examination was unremarkable bilaterally. Spectral domain optical coherence tomography revealed a normal macular retina structure. Visual field examination revealed a superior hemianopsia in the right eye. Head magnetic resonance imaging showed findings compatible with optic neuritis. The visual evoked potentials confirmed the presence of optic neuritis. The patient had been under therapy with adalimumab since January 2014, for Crohn's disease. Suspension of adalimumab was recommended, and it was substituted with tapered deltacortene, from 1 mg/kg/day. After 1 month, the scotoma was resolved completely. CONCLUSIONS: TNFα antagonists can provide benefit to patients with inflammatory autoimmune diseases. However, they can also be associated with severe adverse effects. Therefore, adequate attention should be paid to neurological abnormalities in patients treated with TNFα antagonists.

Biologic Therapy in Inflammatory Eye Conditions (Ophtalmology): Safety Profile.

Non-infectious uveitis can be a potentially sight threatening disease. Very recently, therapeutic strategies have turned towards a new methodology, which includes biologic agents. The introduction of biologic drugs has started a Copernican revolution in ophthalmology: biologic therapies represent a revolutionary option for those patients who present non-responder, sight threatening uveitis. The availability of these therapies has improved the uveitis outcome. The present review shows the most relevant medical literature on biologic agents in ophthalmology, such as tumor necrosis factor blockers, anti-interleukins and other related biologics. Several papers reported the efficacy of biologic agents in a large number of refractory uveitides, which suggest a promising role of biologic drugs for selected cases. On the other hand, the medical literature does not have consistent numbers yet, which hopefully will validate the promising preliminary results. Biologic agents are not only promising drugs for the treatment of nonresponder uveitis, but also they show an apparently favourable safety profile, although several topics remain unsolved: it is still not clear when commencing the treatment, which agent to choose, and the length of biologic therapy. Moreover, the high costs and the still not clear safety profile have very often limited their use only for severe, non-responder uveitis in highly specialized uveitis centres.

STANDARD CUT RATE 25-GAUGE VITRECTOMY VERSUS ULTRAHIGH-SPEED 25-GAUGE SYSTEM IN CORE VITRECTOMY: A Randomized Clinical Trial.

PURPOSE: The aim of this study was to compare the efficiency and safety of ultrahigh-speed cut rate 25-gauge system and standard cut rate 25-gauge vitrectomy system. METHODS: In this single-center, prospective randomized study, all consecutive eyes that underwent 25-gauge vitrectomy at the Eye Clinic of the University of Ancona from September 2014 to November 2014 were randomized to receive 25-gauge vitrectomy with 7,500 cuts per minute (cpm) probes (7,500 Group) or 25-gauge vitrectomy with 5,000 cpm probes (Standard Group). Exclusion criteria were previously vitrectomized eye, trauma cases, retinal detachment with proliferative vitreoretinopathy, and endophthalmitis. Main outcome measure was core vitrectomy duration. Secondary outcome was the incidence of iatrogenic retinal breaks and other complications related to surgery. RESULTS: Overall, 62 eyes were enrolled; 31 eyes received 25-gauge 7,500 cpm vitrectomy and 31 eyes received 25-gauge 5,000 cpm vitrectomy. The duration of core vitrectomy was significantly lower in the 7,500 Group (P = 0.030, t-test for independent samples). Mean ± standard deviation core vitrectomy time was 161.32 ± 39.10 seconds in the 7,500 Group and 184.10 ± 41.69 seconds in the Standard Group. The observed difference in mean core vitrectomy duration between subjects treated with 7,500 cpm probes and those in the Standard Group was equal -22 seconds (95% confidence interval: -43.3 to -2.2). There was no difference in the incidence of iatrogenic breaks between the 2 groups, and there were no other complications over a 3-month follow-up period. CONCLUSION: The 25-gauge 7,500 cpm vitrectomy is an effective and safe surgical procedure, and it can significantly reduce core vitrectomy time in eyes undergoing vitreoretinal surgery.

Comparative study between amniotic-fluid mesenchymal stem cells and retinal pigmented epithelium (RPE) stem cells ability to differentiate towards RPE cells.

Dysfunction of the retinal pigmented epithelium (RPE) is one of the first effects of dry age-related macular degeneration (AMD) with consequent blindness. Hence, patients affected by this retinal disorder could benefit from a cell-based transplantation strategy for RPE. Actually, an effective protocol to approach this problem is lacking, though recently, it has been postulated the existence of a subpopulation of RPE stem cells (RPESCs) derived from adult RPE and able to reconstitute a functional RPE. On the other hand, the evidence related to the differentiative potential of human mesenchymal stem cells (MSCs) is continuously increasing. Among others, amniotic fluid-derived MSCs (AF-MSCs) may be a promising candidate, since these cells are characterized by high proliferation and differentiative potential. In this study, AF-MSCs and RPESCs were isolated, characterized to assay their stemness and induced to neuronal/retinal differentiation; specific RPE markers were then analyzed. Our results indicate that RPESCs are more suitable candidates for RPE replacement than AF-MSCs.

Rescue therapy with intravitreal aflibercept for choroidal neovascularization secondary to choroidal osteoma non-responder to intravitreal bevacizumab and ranibizumab.

To investigate the effect of aflibercept in a rare case of choroidal neovascularization (CNV) secondary to choroidal osteoma (CO) and refractory to ranibizumab and bevacizumab. A 45-year-old male with CO-related CNV in his left eye received prior two intravitreal 1.25 mg bevacizumab injections and three intravitreal 0.5 mg ranibizumab injections without visual and anatomic improvement. Best-corrected visual acuity assessment, ophthalmic examination, fundus photography, and optical coherence tomography (OCT) were performed. Switching to intravitreal injection of 2.0 mg aflibercept was performed. After three loading doses of intravitreal aflibercept, visual acuity of the left eye improved from 20/50 to 20/32. Resolution of the persistent subfoveal fluid and reduction of retinal hemorrhage were confirmed according to ophthalmoscopy and OCT findings. No serious adverse events were observed. The treatment effect persisted during a 10-month follow-up period. In choroidal osteoma, switching to intravitreal aflibercept injection may be an effective therapeutic option for treatment of CNV refractory to ranibizumab and bevacizumab.

TRANSCONJUNCTIVAL NONVITRECTOMIZING VITREOUS SURGERY VERSUS 25-GAUGE VITRECTOMY IN PATIENTS WITH EPIRETINAL MEMBRANE: A Prospective Randomized Study.

PURPOSE: To compare the clinical outcomes and the rate of complications of 27-gauge transconjunctival nonvitrectomizing vitreous surgery (NVS) and of 25-gauge transconjunctival sutureless vitrectomy surgery for idiopathic epiretinal membrane removal. METHODS: In this prospective randomized study, 83 phakic eyes of 83 consecutive patients with an idiopathic epiretinal membrane were randomized to receive 27-gauge NVS (NVS-group) or 25-gauge vitrectomy (Standard-group). Main outcome measures were best-corrected visual acuity, central retinal thickness, nuclear density units' changes, and rate of complications. RESULTS: Thirty-nine eyes of the Standard-group and 40 of the NVS-group were considered in final analysis. Mean best-corrected visual acuity improved significantly in both groups, with a significant better result at 12 months in NVS-group (P = 0.039; t-test). Central retinal thickness decreased significantly in both groups (P < 0.001, Tukey test), without significant difference between the two groups at any time point. At 12 months, nuclear density increased significantly in the Standard-group (analysis of variance, P < 0.001), and it did not change in the NVS-group (analysis of variance, P = 0.537). Epiretinal membrane recurred in 5.1% of eyes in the Standard-group and in 7.5% of eyes in the NVS-group (Fisher's exact test, P = 1.000). CONCLUSION: The 27-gauge NVS is an effective surgical procedure in eyes with epiretinal membrane and it induces less progression of nuclear sclerosis than 25-gauge vitrectomy.

Correlation of preoperative retinal pigment epithelium status with foveal microstructure in repaired macular holes.

PURPOSE: To investigate, with spectral-domain optical coherence tomography, if the preoperative status of the retinal pigment epithelium (RPE) affects the postoperative foveal morphology and visual outcomes in eyes with surgically closed macular holes (MHs). METHODS: In 52 eyes with surgically closed MHs, preoperative RPE morphology was evaluated and graded based on the measurement of the largest hyperreflective protrusions above the RPE line. Foveal microstructural features and best-corrected visual acuity (BCVA) were evaluated 12 months after surgery. RESULTS: At 12 months, a significant correlation was found between postoperative degree of integrity of the photoreceptors with preoperative RPE morphology, and base diameter of the hole (p = 0.003 and p = 0.028, respectively); mean BCVA at 12 months in eyes with diffuse RPE alteration was significantly lower than in eyes with small or no RPE alteration (p < 0.05). CONCLUSIONS: Preoperative RPE integrity may be indicative of good photoreceptor restoration and visual recovery in patients with surgically closed MHs.

25-gauge vitrectomy combined with half-fluence photodynamic therapy for the treatment of juxtapapillary retinal capillary hemangioma: a case report.

A rare case of juxtapapillary retinal capillary hemangioma (JRCH) with tractional macular detachment that was managed successfully with minimally invasive 25-gauge vitreoretinal surgery, followed by two sessions of half-fluence photodynamic treatment (PDT) with good visual outcome, is presented. A 13-year-old female patient had progressive deterioration of the vision of her right eye due to the presence of tractional macular detachment associated with JRCH in von Hippel-Lindau (VHL) disease. A 25-gauge sutureless vitreoretinal surgery was successfully performed. Two months following surgery, the JRCH was treated with two sessions of half-fluence PDT at an interval of 4 months. Visual acuity improved from a preoperative level of 20/50 to 20/25 24 months postoperatively. Resolution of the tractional macular detachment, reduction of papillomacular area fluid, and reduction in size of the JRCH were observed during the follow-up period. No serious adverse events were observed. Small-gauge vitreoretinal surgery followed by PDT can be effective and safe in relieving tractional macular detachment and recovering useful visual acuity in JRCH in VHL disease.

Iatrogenic retinal breaks in 25-gauge vitrectomy under air compared with the standard 25-gauge system for macular diseases.

PURPOSE: To evaluate the incidence rates of iatrogenic retinal breaks in eyes that underwent 25-gauge vitrectomy under air compared with 25-gauge standard vitrectomy for idiopathic macular holes or idiopathic epiretinal membranes. METHODS: In this retrospective, comparative interventional study, 435 eyes were enrolled. In all patients after core vitrectomy and epiretinal/inner limiting membrane peeling, complete vitrectomy of the base was performed, respectively under air (air group) or under fluid infusion (standard group). RESULTS: The number of eyes with iatrogenic retinal breaks was significantly lower in the air group than in standard group (4/197 and 16/238, 2% and 7%, respectively; P = 0.035). A postoperative retinal detachment developed in 2 eyes (1%) in the standard group, and in no eyes of the air group (0%). Factors related to the occurrence of retinal breaks were surgically induced posterior vitreous detachment (P = 0.006), standard vitrectomy (P = 0.023), and surgery for macular hole (P = 0.030). CONCLUSION: The 25-gauge vitrectomy under air is associated with a lower incidence rate of retinal breaks compared with the standard 25-gauge vitrectomy.

Atypical presentation of antiphospholipid syndrome: a case report.

We report an atypical presentation of Antiphospholipid syndrome (APS) with concomitant subhyaloid hemorrhage, engorged and tortuous retinal veins, intraretinal hemorrhages, and cotton wool spots in a 38-year-old female. Medical treatment was preferred to any invasive treatment. The subhyaloid hemorrhage resolved spontaneously and the patient recovered a visual acuity of 20/20 in her right eye 3 months after the initial episode. A prompt diagnosis of this condition is fundamental to consider a systemic treatment to avoid any further thrombosis.

Juxtapapillary retinal capillary hemangioma: new therapeutic strategies.

The treatment of juxtapapillary retinal capillary hemangiomas (JRCHs) is still a therapeutic dilemma without established guidelines. Because of the location of these hemangiomas on or adjacent to the optic nerve, treatment is difficult and complex, especially when JRCHs are located in the papillomacular bundle. This manuscript reviews the clinically relevant data on literature regarding the treatment of JRCHs, focusing on novel combined therapies that have shown promising results in these lesions.

Epiretinal membrane surgery for combined hamartoma of the retina and retinal pigment epithelium: role of multimodal analysis.

BACKGROUND: The purpose of this study was to evaluate the role of spectral domain optical coherence tomography (SD-OCT), MP-1 microperimetry, and fundus autofluorescence imaging for planning surgical procedures in combined hamartomas of the retina and retinal pigment epithelium (CHR-RPE) and following epiretinal membrane removal. METHODS: In an interventional retrospective case series, six consecutive subjects with CHR-RPE underwent vitrectomy and epiretinal membrane peeling, with 4 years of follow-up. Each underwent complete ophthalmic examination, including best corrected visual acuity, fundus examination, fundus fluorescein angiography, SD-OCT, MP-1, and fundus autofluorescence at one, 6, 12, and 48 months. RESULTS: Six eyes from six subjects with CHR-RPE were studied (mean age 31 ± 14 years). All patients were phakic and five were male (83.3%). Lesions were unilateral, ie, three macular, two juxtapapillary and macular, and one pericentral. Preoperative best corrected visual acuity was 0.3 ± 0.08 Snellen, with significant improvement to 0.9 ± 0.17 Snellen (P = 0.001) at 4 years of follow-up. Mean retinal sensitivity within the central 20° field improved from 16.6 ± 1.84 dB to 18.8 ± 0.96 dB (P = 0.07). There was also a statistically significant reduction in the visual defect (P = 0.04). SD-OCT demonstrated that the epiretinal membranes were completely removed in all but one patient, with significantly decreased macular edema on follow-up at one, 6, 12, and 48 months (P = 0.001). A positive correlation was shown between preoperative macular sensitivity and postoperative best corrected visual acuity. Fundus autofluorescence demonstrated a block in background autofluorescence at the site of the lesion, and hyperautofluorescence at the edematous retina overlain by the epiretinal membrane. CONCLUSION: Surgery is an effective treatment for CHR-RPE. SD-OCT, fundus autofluorescence, and MP-1 are valuable and noninvasive tools to guide surgical procedures for CHR-RPE. To the best of our knowledge, this study represents the first use of MP-1 in CHR-RPE in conjunction with SD-OCT and fundus autofluorescence imaging for better guided surgery as well as anatomical and functional prognosis.