Combined therapy with intravitreal aflibercept and subtenon corticosteroids in eyes with severe diabetic papillopathy: two case reports.

BACKGROUND: Diabetic papillopathy is a rare diagnosis of exclusion characterized by unilateral or bilateral optic disc edema with variable degrees of visual loss. Although the visual prognosis has been generally reported as favorable, the presence of severe disc edema associated with macular edema prompts the need for treatment. We present a specific and unreported therapeutic approach consisting of intravitreal aflibercept and subtenon triamcinolone acetonide injections in two patients with evidence of diabetic papillopathy and macular edema. CASE PRESENTATION: In the first case, a 60-year-old Caucasian woman affected by type II diabetes mellitus presented with fundoscopic evidence of sequential bilateral optic disc edema associated with acute severe visual loss in both eyes. The second patient, a diabetic 57-year-old Caucasian male, presented with sudden painless visual loss in his left eye. Multimodal imaging and systemic findings correlated towards an infrequent diagnosis of diabetic papillopathy. In a period of 5-7 weeks after treatment, both patients experienced almost full visual and anatomical recovery. A steady situation was observed at 12 months of follow-up. CONCLUSIONS: Both our cases displayed a severe grade of optic disc edema, which was optimally reversed with intravitreal aflibercept and subtenon triamcinolone acetonide leading to a relatively rapid and safe improvement in visual acuity.

Photodynamic therapy and subthreshold micropulse laser treatment - A novel combined approach for the treatment of serous retinal detachment in dome-shaped macula.

Dome-shaped macula (DSM) is characterized by an inward convexity of the macula in myopic eyes, as visualized on optical coherence tomography (OCT). Serous retinal detachment (SRD) is a common complication of DSM, leading to a deterioration of visual acuity, in association with retinal pigment epithelium (RPE) atrophic changes. Many different therapeutic approaches to SRD secondary to DSM have been attempted, with variable results. We report our experience (11 treatment-naïve patients) with a combined new treatment approach, using half-fluence and half-dose photodynamic therapy (PDT) followed by subthreshold 577 nm micropulse laser treatment (STLT), for SRD related to DSM after a 6-month follow-up. Central foveal thickness was significantly decreased at the end of the follow-up. SRD diminished in all cases, and 5 eyes (45.4 %) registered complete resolution at the end of the 6-month follow-up, while 6 eyes (54.5 %) experienced two lines of improvement in BCVA at the end of the follow-up. No case showed postoperative complications. Therefore, this represents the first study evaluating the visual and anatomical outcomes of a safe and effective combined treatment of SRD in DSM.

Multimodal Imaging Analysis of Acute Syphilitic Posterior Placoid Chorioretinitis: A Case Report.

The authors report a multimodal imaging analysis of a case of acute syphilitic posterior placoid chorioretinitis (ASPPC) occurring in a 51-year-old man. Best-corrected visual acuity (BCVA) was 0.5 and 0.8 in the right and left eyes, respectively. The authors performed spectral-domain optical coherence tomography, fundus autofluorescence, fluorescein angiography, and indocyanine green angiography. All of the examinations were suggestive of the diagnosis of ASPPC, a rare manifestation of syphilis that has distinctive anatomical characteristics that are detectable early on with multimodal imaging. Moreover, serological tests were positive for syphilis infection, so the patient received intravenous penicillin G for 14 days. Final BCVA was 1.0 in the right eye and 0.9 in the left eye. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e179-e184.].

Management of diabetic macular edema with intravitreal dexamethasone implants: Expert recommendations using a Delphi-based approach.

OBJECTIVES:: Despite being approved and effective, steroids, and especially dexamethasone intravitreal implants, still have a poorly-defined role in management of diabetic macular edema. In order to overcome some of the limitations in current recommendations, a group of experts met to define consensus on some of the most controversial issues on the use of dexamethasone intravitreal implants in daily management of diabetic macular edema. METHODS:: A Delphi-based approach was utilized to develop clinically relevant statements applicable to routine treatment settings. A Steering Committee composed of four experts formulated 30 relevant statements, which were voted upon by a panel of 40 ophthalmologists/retinal specialists from across Italy. RESULTS:: Dexamethasone intravitreal implants were considered to be a valid first-line alternative to treatment with an anti-vascular endothelial growth factor agent and should be the first choice in pseudophakic and vitrectomized patients. A Pro Re Nata regimen was felt to be appropriate for retreatment with dexamethasone intravitreal implants while a 6-month waiting period was not considered suitable. Among steroid treatments, dexamethasone intravitreal implants were considered to have the best ocular tolerability. In patients with persistent macular edema after the loading-phase treatment with an anti-vascular endothelial growth factor, consensus was reached that clinicians should consider switching therapy to dexamethasone intravitreal implants. Moreover, dexamethasone intravitreal implants can reduce the treatment burden for individuals who are not able to cope with the more intensive treatment regimen required by anti-vascular endothelial growth factor therapy. CONCLUSIONS:: While further studies are needed, this survey provides some key recommendations for clinicians treating diabetic macular edema that may be useful when choosing dexamethasone intravitreal implants in daily practice.

Idiopathic Acute Exudative Polymorphous Vitelliform Maculopathy: Clinical Spectrum and Multimodal Imaging Characteristics.

PURPOSE: To describe clinical findings in patients with acute exudative polymorphous vitelliform maculopathy (AEPVM). DESIGN: Retrospective, observational, multicenter case series review. PARTICIPANTS: Consecutive patients diagnosed with idiopathic AEPVM. METHODS: Review of clinical charts, multimodal imaging, electrophysiologic findings, and genetic findings in previously unpublished patients and review of the literature. MAIN OUTCOME MEASURES: Clinical features of idiopathic AEPVM and differential diagnosis. RESULTS: Eighteen patients (age range, 21-74 years) with typical features of AEPVM, including initial localized, serous detachments followed by the development of characteristic yellow-white deposits in the vitelliform space. Over time, this hyperautofluorescent material gravitated within the larger lesions, resulting in typical curvilinear deposits characteristic of later stages. Symptoms and clinical findings lasted from weeks to several years. Some patients showed previously undescribed features such as fluorescein-negative intraretinal cystic changes, choroidal neovascularization, serous retinal elevations mimicking retinal folds, increased choroidal thickness, lack of rapid visual recovery, and recurrence years after complete resolution of initial manifestations. CONCLUSIONS: Acute exudative polymorphous vitelliform maculopathy can present with a more variable natural course than previously described. Paraneoplastic retinopathy and autosomal recessive bestrophinopathy closely resemble AEPVM, necessitating medical and hereditary evaluation to exclude these clinical possibilities. This series of patients with AEPVM expands the clinical spectrum of the disorder, including demographics, clinical manifestations, imaging features, natural course, and visual prognosis.

Acute macular neuroretinopathy associated with subclinical cytomegalovirus infection.

PURPOSE: To report a case of bilateral acute macular neuroretinopathy (AMN) occurring in a 32-year-old woman, analyzed using the multimodal imaging technique. CASE REPORT: A 32-year-old Caucasian woman presented with 20 days history of acute onset of blurred vision in the right eye. The best-corrected visual acuity (BCVA) was 0.8 and 1.0 in the right and left eyes, respectively. She reported a lower urinary tract infection associated with fever, 7 days before the onset of the ocular symptoms. Serological tests demonstrated the presence of IgM specific for cytomegalovirus (CMV), while all the other laboratory tests were negative. SD-OCT exhibited the disruption of the inner segment-outer segment junction, associated with hyper-reflectivity of a thickened outer plexiform layer overlying such area associated with thinning of the outer nuclear layer. The patient was diagnosed with AMN and received a corticosteroid treatment. During all the follow-up, OCT features did not change, although BCVA improved. Four months after the first visit, we found also in the left eye a subfoveal IS/OS disruption but differently from the right eye, in which the abnormalities persisted during all the follow-up visits, in the left one they disappeared only after a month. The IgM specific for the CMV remained positive during the whole follow-up. CONCLUSIONS: To our knowledge, this is the first patient reported with a diagnosis of AMN associated with persisting presence of IgM specific for CMV.

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.

A Case of Goldenhar Syndrome Associated with a New Retinal Presentation: Exudative Vitelliform Maculopathy.

Goldenhar syndrome is a rare clinical disturbance with a wide range of clinical manifestations. We report on a 6-year-old male with peculiar retinal presentation of Goldenhar syndrome. The patient was referred to Ophthalmology for central scotoma in the left eye, where visual acuity was 20/100. Fundus examination was unremarkable, except for yellowish material in the central macula. SD-OCT revealed interruption of the external limiting membrane and inner and outer segment junctions, with disorganized material in the vitelliform space and subretinal fluid. Six months later, fundus and SD-OCT examinations were unchanged without treatment, but visual acuity in the left eye had improved to 20/50. Five years later, he had similar clinical manifestations in the right eye. He was started on systemic steroids. After 15 days, his visual acuity improved to 20/20 and subretinal fluid and yellowish material in the vitelliform space disappeared. Goldenhar syndrome has variable presentation, including vitelliform maculopathy.

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.

Considering photodynamic therapy as a therapeutic modality in selected cases of dome-shaped macula complicated by foveal serous retinal detachment.

BACKGROUND AND OBJECTIVE: To study the role of photodynamic therapy (PDT) as a therapeutic modality in myopic patients with dome-shaped macula (DSM) associated with foveal serous retinal detachment (SRD). PATIENTS AND METHODS: Retrospective interventional case series. The medical records of 10 consecutive myopic patients (10 eyes) with DSM associated with subfoveal SRD and treated with PDT were reviewed. Visual gain and loss were considered as increasing or decreasing of two or more lines of best corrected visual acuity (BCVA), respectively, and eyes with fluid resolution were deemed responsive to PDT. RESULTS: All eyes underwent several PDT treatments, with a median of three and a median follow-up time of 15.5 months. At final follow-up, six eyes (60%) showed complete resolution of the foveal SRD. The baseline hypocyanescent macular area observed during late indocyanine green angiography (ICGA) frames was significantly lower in the group of patients who responded to PDT and had an increase of at least two Snellen lines in BCVA (P = .01). CONCLUSION: Data suggest that myopic eyes associated with DSM and foveal SRD may be responsive to PDT, showing total resolution of fluid accumulation and positive BCVA changes if baseline ICGA findings show evidence of a limited hypocyanescent macular area.

New best1 mutations in autosomal recessive bestrophinopathy.

PURPOSE: To report the ocular phenotype in patients with autosomal recessive bestrophinopathy and carriers, and to describe novel BEST1 mutations. METHODS: Patients with clinically suspected and subsequently genetically proven autosomal recessive bestrophinopathy underwent full ophthalmic examination and investigation with fundus autofluorescence imaging, spectral domain optical coherence tomography, electroretinography, and electrooculography. Mutation analysis of the BEST1 gene was performed through direct Sanger sequencing. RESULTS: Five affected patients from four families were identified. Mean age was 16 years (range, 6-42 years). All affected patients presented with reduced visual acuity and bilateral, hyperautofluorescent subretinal yellowish deposits within the posterior pole. Spectral domain optical coherence tomography demonstrated submacular fluid and subretinal vitelliform material in all patients. A cystoid maculopathy was seen in all but one patient. In 1 patient, the location of the vitelliform material was seen to change over a follow-up period of 3 years despite relatively stable vision. Visual acuity and fundus changes were unresponsive to topical and systemic carbonic anhydrase inhibitors and systemic steroids. Carriers had normal ocular examinations including normal fundus autofluorescence. Three novel mutations were detected. CONCLUSION: Three novel BEST1 mutations are described, suggesting that many deleterious variants in BEST1 resulting in haploinsufficiency are still unknown. Mutations causing autosomal recessive bestrophinopathy are mostly located outside of the exons that usually harbor vitelliform macular dystrophy-associated dominant mutations.

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.

Successful treatment of an overlapping choriocapillaritis between multifocal choroiditis and acute zonal occult outer retinopathy (AZOOR) with adalimumab (Humira™).

To report a case of overlapping choriocapillaritis that initially presented as multifocal choroiditis (MFC) but later showed features compatible with acute zonal occult outer retinopathy (AZOOR) resistant to standard immunosuppression that responded only to adalimumad therapy. A 41-year-old patient presented with multiple small, discrete yellow-whitish spots in both eyes, compatible with MFC. A few weeks later, despite treatment with sub-Tenon and systemic corticosteroids, a choroidal neovascularization occurred in the right eye. The patient was treated with intravitreal anti-vascular endothelial growth factor. After 2 months, reduced visual acuity, photopsia and visual field defect in the left eye occurred. Spectral domain optical coherence tomography revealed photoreceptor outer segment defects common to all choriocapillaritis. The additional finding of an annular scotoma and a 360° ring on indocyanine green angiography led us to make the diagnosis of presumed AZOOR. Despite the combination of several immunosuppressive agents leading to temporary control of the disease, the patient experienced a further worsening. At that point, adalimumab was introduced, which led to an obvious improvement. This case supports the hypothesis that two different entities of the so-called AZOOR complex can be possible in the same eye, even asynchronously. In our case, anti-tumor necrosis factor alpha monoclonal antibody therapy represented a valid treatment option in a patient unresponsive to traditional immunosuppressive treatments.

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.