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.

Acute Zonal Occult Outer Retinopathy (AZOOR) Results from a Clinicopathological Mechanism Different from Choriocapillaritis Diseases: A Multimodal Imaging Analysis.

BACKGROUND AND AIM: AZOOR is a rare disease characterized by loss of zones of outer retinal function, first described by J Donald Gass in 1993. Symptoms include acute onset photopsias and subjective visual field losses. The syndrome is characterized by a normal fundus appearance, scotomas and electroretinographic changes pointing towards outer retinal dysfunction. Evolution, response to immunosuppressive treatment and outcome are difficult to predict. The aim of this small case series was to identify the morphological changes and sequence of events in AZOOR thanks to multimodal imaging. METHODS: Charts of AZOOR patients seen in the Centre for Ophthalmic Specialized care (COS, Lausanne, Switzerland) were analyzed by multimodal imaging including fundus photography, fluorescein angiography (FA), indocyanine green angiography (ICGA), blue light fundus autofluorescence (BL-FAF) and spectral domain optical coherence tomography (SD-OCT) in addition to a complete ophthalmological examination including visual field testing and microperimetry, as well as OCT angiography (OCT-A) and ganglion-cell complex analysis when available. Cases and Results: Three AZOOR patients with a mean follow-up of 47 ± 25.5 months were included following the clinical definitions laid down by J Donald Gass. The primary damage was identified at the level of the photoreceptor outer segments with an intact choriocapillaris and retinal pigment epithelium (RPE) layer, these structures being only secondarily involved with progression of the disease. CONCLUSION: Although AZOOR has often been included within white dot syndromes, some of which are now known to be choriocapillaris diseases (choriocapillaritis entities), our findings clearly commend to differentiate AZOOR from entities such as MEWDS (Multiple evanescent white dot syndrome), APMPPE (Acute Posterior Multifocal Placoid Pigment Epitheliopathy), MFC (Multifocal Choroiditis) and others, as the damage to photoreceptors is primary in AZOOR (a retinopathy) and secondary in choriocapillaritis (a choriocapillaropathy).

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.

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.

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.

Long-term control of non-infectious paediatric panuveitis refractory to traditional immunesuppressive therapy, successfully treated with Adalimumab (HumiraTM).

OBJECTIVES: The aim of this paper is to present two cases of severe idiopathic non-infectious paediatric panuveitis, unresponsive to traditional therapy, successfully treated with Adalimumab (HumiraTM, Abbott Pharmaceutical Inc.) in the long term. METHODS: The data of the two cases are presented and the literature is reviewed. RESULTS: At base line, case 1 had 0.2 in the RE and 0.5 in the LE, while case 2 had 0.5 and 0.4 in the RE and LE, respectively. The anterior chamber (AC) of case 1 had 3+ cells and 3+ flare in both eyes, as well as diffuse keratic precipitates (Kps). Case 2 presented 2+ cells and 3+ flare in both eyes, as well as tiny Kps in the inferior part of the endothelium. The Binocular Indirect Ophthalmoscopy (BIO) score was +2 in both eyes of case 1 and case 2 at first examination. After Adalimumab initiation, both patients presented a dramatic resolution of the ocular inflammation, as well as a rapid improvement of the BCVA. Case 1 had 0.8 and 1.0 in the RE and the LE, respectively, while case 2 presented 1.0 in both eyes. At the last visit, both patients presented a quiet uveitis and stable BCVA: case 1 had 0.8 and 1.0 in the RE and the LE, respectively, while case 2 presented 1.0 in both eyes. No side effects were recorded during this time. CONCLUSIONS: Adalimumab can be a promising drug for the therapy of severe, refractory paediatric uveitis, although further studies are needed on its application in uveitis.

Anti vascular endothelial growth factor sequential therapy for neovascular age-related macular degeneration: is this the new deal?

OBJECTIVE: To review clinical data on the sequential use of the non-selective vascular endothelial growth factor (VEGF) inhibitors (ranibizumab and bevacizumab) and the selective VEGF inhibitor (pegaptanib) in the treatment of neovascular age related macular degeneration (n-AMD). METHODS: This is a selective review of the literature based on a PubMed search using the terms 'age-related macular degeneration', 'selective anti-VEGF', 'non-selective anti-VEGF' and 'combination therapy' from 2000 to date in the English language. Studies on the management of n-AMD reporting adherence, patient-reported outcomes, costs, side effects, resource use and cost effectiveness were also included. RESULTS: The trial data suggest that pan-VEGF inhibition provides improved treatment outcomes in patients with n-AMD with selective anti-VEGF agents offering better tolerability on long-term treatment. A pilot trial and a large-scale, multicentre study confirmed the long-term efficacy of a selective VEGF inhibitor when used as maintenance therapy. Importantly, there is evidence that selective VEGF inhibition also reduces the risks associated with pan-VEGF blockade in patients with n-AMD. DISCUSSION: Anti-VEGF agents play a principal role in the management of n-AMD. The most potent are the pan-VEGF agents although there is some discussion regarding their long-term tolerability. The sequential use of non-selective VEGF inhibitors as booster therapy with a selective VEGF inhibitor as maintenance therapy seems to offer a promising safety/efficacy profile, as well as improved cost/effectiveness.

Biologic agents in inflammatory eye disease.

Non-infectious uveitis is a potentially sight threatening disease. Along the years, several therapeutic strategies have been proposed as a means to its treatment, including local and systemic steroids, immunosuppressives and more recently, biologic agents. The introduction of biologics can be defined as a new era: biologic therapies provide new options for patients with refractory and sight threatening inflammatory disorders. The availability of such novel treatment modalities has markedly improved the therapy of uveitis and considerably increased the possibility of long-term remissions. This article provides a review of current literature on biologic agents, such as tumor necrosis factor blockers, anti-interleukins and other related biologics, such as interferon alpha, for the treatment of uveitis. Several reports describe the efficacy of biologics in controlling a large number of refractory uveitides, suggesting a central role in managing ocular inflammatory diseases. However, there is still lack of randomized controlled trials to validate most of their applications. Biologics are promising drugs for the treatment of uveitis, showing a favorable safety and efficacy profile. On the other hand, lack of evidence from randomized controlled studies limits our understanding as to when commence treatment, which agent to choose, and how long to continue therapy. In addition, high cost and the potential for serious and unpredictable complications have very often limited their use in uveitis refractory to traditional immunosuppressive therapy.