Cheryl A. Arcinue

A Comparison Between the Fluocinolone Acetonide (Retisert) and Dexamethasone (Ozurdex) Intravitreal Implants in Uveitis

PURPOSE To evaluate the efficacy and safety of the fluocinolone acetonide (Retisert) implant compared with the dexamethasone (Ozurdex) implant in patients with noninfectious uveitis. DESIGN Comparative case series. STUDY PARTICIPANTS Twenty-seven eyes received either the fluocinolone acetonide (FA) (n=16) or dexamethasone (n=11) implant. METHODS Chart review of patients at the Massachusetts Eye Research and Surgery Institution (MERSI) was done and patients were selected and matched according to age, sex, and type of uveitis. Eyes that received either the FA or dexamethasone implant, with follow-up ranging from 6 months to 2 years, were included. MAIN OUTCOME MEASURE The recurrence rate of uveitis after implantation. RESULTS There were no significant differences in the baseline demographic characteristics. The majority of cases were idiopathic panuveitis, with 36.4% and 31.3% of eyes in the Ozurdex and Retisert groups, respectively. Recurrence rates of uveitis were 1.7 and 0.5 per 100 person-months in the Retisert and Ozurdex groups, respectively, with Retisert-implanted eyes 3.16 times more at risk of recurrence; however, this difference was not statistically significant (P=0.41). No significant differences were seen in terms of improvement in inflammatory score and best-corrected visual acuity (BCVA). The median survival time for a second implant was 13 and 28 months for the Ozurdex and Retisert groups, respectively (P=0.0028). Eyes with the Ozurdex were 5 times more likely to receive a second implant (P=0.02). No eyes in the Ozurdex group needed additional glaucoma medications, surgery, or laser compared to 44% of eyes in the Retisert group. Eyes with the Retisert implant had a statistically higher rate of having more glaucoma medications, surgery, or laser (P=0.02). In the Ozurdex group, 50% of phakic eyes at baseline had cataract progression and subsequent surgery compared with 100% of Retisert phakic eyes. Eyes with the Retisert implant are 4.7 times more at risk of cataract progression (P=0.04). CONCLUSIONS The dexamethasone (Ozurdex) implant seems comparable to the fluocinolone acetonide (Retisert) implant in preventing recurrence of noninfectious uveitis and in improving inflammation and BCVA. However, there were higher rates of cataract progression and need for glaucoma medications, laser, and surgery with the Retisert implant.

One-Year Outcomes of Aflibercept in Recurrent or Persistent Neovascular Age-Related Macular Degeneration

PURPOSE To evaluate 6-month and 1-year outcomes of every-8-weeks (Q8W) aflibercept in patients with resistant neovascular age-related macular degeneration (AMD). DESIGN Retrospective, interventional, consecutive case series. METHODS Retrospective review of patients with resistance (multiple recurrences or persistent exudation) to every-4-weeks (Q4W) ranibizumab or bevacizumab that were switched to Q8W aflibercept. RESULTS Sixty-three eyes of 58 patients had a median of 13 (interquartile range [IQR], 7-22) previous anti-vascular endothelial growth factor (anti-VEGF) injections. At 6 months after changing to aflibercept, 60.3% of eyes were completely dry, which was maintained up to 1 year. The median maximum retinal thickness improved from 355 μm to 269 μm at 6 months (P < .0001) and 248 μm at 1 year (P < .0001). There was no significant improvement in ETDRS visual acuity at 6 months (P = .2559) and 1 year follow-up (P = .1081) compared with baseline. The mean difference in ETDRS visual acuity compared to baseline at 6 months was -0.05 logMAR (+2.5 letters) and 0.04 logMAR at 1 year (-2 letters). CONCLUSION Sixty percent of eyes with resistant AMD while on Q4W ranibizumab or bevacizumab were completely dry after changing to Q8W aflibercept at the 6-month and 1-year follow-ups, but visual acuity did not significantly improve. Only a third of eyes needed to be switched from Q8W to Q4W aflibercept owing to persistence of fluid; Q8W dosing of aflibercept without the initial 3 monthly loading doses may be a good alternative in a select group of patients who may have developed ranibizumab or bevacizumab resistance.

Optical coherence tomography findings of the vitreoretinal interface in asymptomatic fellow eyes of patients with acute posterior vitreous detachment.

Purpose: To describe the vitreoretinal interface of the asymptomatic fellow eyes of patients with acute unilateral posterior vitreous detachment (PVD) based on biomicroscopic examination and spectral domain optical coherence tomography. Methods: Sixty-five eyes of 65 consecutive patients with acute unilateral PVD were examined by slit-lamp, indirect ophthalmoscopy, and spectral domain optical coherence tomography. The state of PVD in different retinal locations and premacular pocket were assessed and graded using spectral domain optical coherence tomography. Results: Nine eyes (13.85%) had no PVD, 15 (23.08%) had extrafoveal vitreous separation (Stage 1), 18 (27.69%) had partial foveal vitreous separation (Stage 2), 12 (18.46%) had complete foveal vitreous separation (Stage 3), and 11 (16.92%) had a complete PVD (Stage 4). The presence of a premacular pocket showed equal distribution in Stages 0, 1, and 2 (66.67, 80.00, and 77.78%, respectively) but was significantly less common in Stages 3 (P = 0.016) and 4 (P < 0.0001). Only certain posterior vitreous configurations were identified (P < 0.0001), suggesting an orderly progression of PVD evolution. Conclusion: Our spectral domain optical coherence tomography-based PVD staging system describes the evolution of PVDs. This can be used as a guide in predicting the occurrence and evolution of PVD in this population.

Retinal Thickening and Photoreceptor Loss in HIV Eyes without Retinitis

Purpose To determine the presence of structural changes in HIV retinae (i.e., photoreceptor density and retinal thickness in the macula) compared with age-matched HIV-negative controls. Methods Cohort of patients with known HIV under CART (combination Antiretroviral Therapy) treatment were examined with a flood-illuminated retinal AO camera to assess the cone photoreceptor mosaic and spectral-domain optical coherence tomography (SD-OCT) to assess retinal layers and retinal thickness. Results Twenty-four eyes of 12 patients (n = 6 HIV-positive and 6 HIV-negative) were imaged with the adaptive optics camera. In each of the regions of interest studied (nasal, temporal, superior, inferior), the HIV group had significantly less mean cone photoreceptor density compared with age-matched controls (difference range, 4,308–6,872 cones/mm2). A different subset of forty eyes of 20 patients (n = 10 HIV-positive and 10 HIV-negative) was included in the retinal thickness measurements and retinal layer segmentation with the SD-OCT. We observed significant thickening in HIV positive eyes in the total retinal thickness at the foveal center, and in each of the three horizontal B-scans (through the macular center, superior, and inferior to the fovea). We also noted that the inner retina (combined thickness from ILM through RNFL to GCL layer) was also significantly thickened in all the different locations scanned compared with HIV-negative controls. Conclusion Our present study shows that the cone photoreceptor density is significantly reduced in HIV retinae compared with age-matched controls. HIV retinae also have increased macular retinal thickness that may be caused by inner retinal edema secondary to retinovascular disease in HIV. The interaction of photoreceptors with the aging RPE, as well as possible low-grade ocular inflammation causing diffuse inner retinal edema, may be the key to the progressive vision changes in HIV-positive patients without overt retinitis.

Outer retinal tubulations response to anti-VEGF treatment

Aim To review the longitudinal changes of outer retinal tubulations (ORTs) in wet age-related macular degeneration (AMD) and their response to anti-vascular endothelial growth factor (VEGF) therapy by spectral-domain optical coherence tomography (SD-OCT), and to correlate these observations with disease activity, presence or absence of fluid, and patients’ demographics. Methods Retrospective study of wet AMD eyes treated with anti-VEGF agents and showing ORTs on SD-OCT, and the patients’ fellow eye with wet AMD but without ORTs. Results Fifty-one wet AMD eyes from 31 patients diagnosed and treated for wet AMD were included in the review and analysis of data; 33 eyes showed ORTs at baseline, while 18 fellow eyes had no ORTs. During a median follow-up treatment period of 11 months, 23 eyes had stable ORTs and 10 eyes had ORT changes. Among the 10 eyes with ORTs changes, ORTs collapsed during anti-VEGF treatment in 5 eyes but then reappeared within 12 months after stopping treatment. In two eyes, ORTs increased in size during anti-VEGF treatment, while in two other eyes ORTs collapsed without any treatment. In a single eye, ORTs collapsed within 10 months of no treatment and did not reappear upon recurrence of fluid. Eyes with ORTs tended to have lower visual acuity than eyes with no ORTs due to greater disruption of the external limiting membrane in the fovea. Conclusions ORTs documented by SD-OCT may exhibit multiple types of longitudinal changes, such as collapse, recurrence or enlargement, which could be associated with anti-VEGF treatment or spontaneous. Some ORTs may have a vascular component or may be vascular in nature, considering their response to anti-VEGF treatment, while other ORTs are likely composed only of degenerating photoreceptor cells and may collapse independently from anti-VEGF treatments.

Diagnostic Criteria for Primary Ocular Lymphoma

We describe a patient whose diagnosis and treatment of primary intraocular (PIOL) and central nervous system lymphoma (PCNSL) were delayed as a result of strict adherence to a diagnostic criterion of cytologic malignancy features of cells. A 57-year-old woman had a 6-month history of blurred vision and floaters. A diagnostic vitrectomy was performed on her right eye in September 2009, which was positive for monoclonality with IgH gene rearrangement by polymerase chain reaction (PCR); Toxoplasma gondii DNA was also discovered. Cranial magnetic resonance imaging (MRI) was normal. She was started on a combination of antibiotics and prednisone. Despite treatment, her vision continued to decline and floaters appeared in her better (left) eye. The patient was first seen at MERSI in October 2009. Visual acuities (VA) were 20/80 in her right eye and 20/50 in her left eye. The anterior chambers were quiet in both eyes, with 2.5 vitreous cells in her left eye. Bilateral RPE hypertrophy and nummular retinal infiltrates were seen (Fig 1, available at http://aaojournal.org). Initial consideration was bilateral diffuse uveal melanocytic proliferation, with concern for lymphoma. A diagnostic vitrectomy her left eye contained no atypical lymphoid cells but IgH gene rearrangement was again demonstrated. Extensive workup was unrevealing for any infectious, autoimmune, or neoplastic cause. Two weeks after the diagnostic vitrectomy, results of the cytokine analysis revealed a very high interleukin (IL)-10 to IL-6 ratio. Based on the clinical findings, combined with the 2 diagnostic vitrectomy findings of monoclonality with IgH gene rearrangement, and high IL-10 to IL-6 ratio in the vitreous, we believed that the patient had PIOL despite the absence of malignant cells. It was the consensus of the MERSI team, the patient’s local ophthalmologist, and the neuro-oncologist of the Massachusetts General Hospital, to commit to the diagnosis of PIOL and to recommend high-dose intravenous methotrexate (MTX). In the meantime, intravitreal MTX injections were given bilaterally, resulting in vision improvement. When the patient returned to her country, the neuro-oncologists were unwilling to administer MTX because of lack of cytologic proof. In February 2010, the patient developed neurologic symptoms. Brain MRI revealed multiple lesions (Fig 2, available at http:// aaojournal.org) and biopsy revealed a uniform neoplasm composed of small cells with round nuclei and scant cytoplasm, confirming the diagnosis of diffuse large B-cell PCNSL. High-dose intravenous MTX (8 g/m) and rituximab were given, along with multiple bilateral intravitreal MTX injections. With therapy, the patient’s vision and memory returned to baseline. Repeat MRI showed no evidence of tumor. On her last examination in April 2012, the patient displayed no neurologic deficits. Her visual acuity was 20/30 in her right eye and 20/20 in her left eye, with quiet anterior and posterior chambers in both. Her right fundus had diffuse chorioretinal atrophy and pigmentation. Approximately 15% to 25% of PCNSL patients develop ocular manifestations, and 65% to 90% of PIOL patients develop neurologic disease. This is the rationale for prophylactic doses of MTX in patients exhibiting merely ocular disease, an approach that significantly reduces neurologic involvement. The “gold standard” for diagnosing PIOL is the identification of malignant cells in the eye, usually through diagnostic vitrectomy. The National Eye Institute demonstrated that 30% of PIOL cases have had previous false-negative sampling. Monoclonality supports the cytologic diagnosis of lymphoma and is observed using immunohistochemistry, flow cytometry, or PCR to detect IgH gene rearrangements in B-cell lymphoma. Chan et al have shown that 100% of 85 PIOL cases had IgH gene rearrangements using PCR. An IL-10 to IL-6 ratio 1 is highly suggestive of B-cell PIOL; this correctly identified 74.7% of suspected PIOL cases in a study by Chan et al. It has been the consensus that repeating diagnostic vitrectomies, lumbar punctures, or biopsies should be performed until malignant cells are found because “definitive tissue diagnosis is required for initiation of treatment.” As illustrated by this case and others in our personal experience, we disagree with this dogma. We believe that when there is a very strong clinical suspicion of lymphoma, and all other possible etiologies have been excluded, and adjunctive examinations provide evidence for lymphoma, the patient should be afforded the opportunity to decide between observation and aggressive lymphoma treatment. We believe that the demonstration of monoclonality with IgH gene rearrangement together with IL level analysis support the diagnosis of PIOL with a high degree of certainty and should lead to prophylactic MTX-based therapy despite absent cytologic malignant cells in vitreal material. One might ask, “How often is it that unneeded therapy (high-dose MTX or other) might end up being given to a patient who does not have intraocular lymphoma?” This is obviously unanswerable, but in this author’s opinion, it is time to begin the conversation on this matter, rather than to cling to what may now be outdated diagnostic and therapeutic criteria.

Acute unilateral toxoplasma retinochoroiditis associated with adalimumab, a tumor necrosis factor-α antagonist.

PURPOSE The purpose of this study was to report a case of a patient with unilateral toxoplasma retinochoroiditis while on treatment with adalimumab, an anti-tumor necrosis factor α agent for ulcerative colitis. METHODS This is a descriptive case report. RESULTS AND DISCUSSION In addition to the patient with toxoplasma retinochoroiditis, there is one published report of two patients who developed toxoplasma chorioretinitis while on anti-tumor necrosis factor α therapy for rheumatoid arthritis: one was on adalimumab and methotrexate and the other one was on etanercept and methotrexate. CONCLUSION The authors need to be aware of this potentially vision threatening risk with anti-tumor necrosis factor α therapy.

RECALCITRANT CYSTOID MACULAR EDEMA AFTER PARS PLANA VITRECTOMY.

Purpose: To evaluate the outcomes of different types of treatment of chronic cystoid macular edema (CME) after pars plana vitrectomy. Methods: Retrospective review of eyes that developed chronic CME after pars plana vitrectomy treated with intravitreal triamcinolone acetonide (TCA) with or without the addition of anti-vascular endothelial growth factor. Results: Thirty-nine eyes of 37 patients were included, with a median duration between pars plana vitrectomy and onset of CME of 5 months (interquartile range, 3–12). In most eyes (66.7%), the main indication for surgery was for vitreomacular interface disorders, such as epiretinal membrane, vitreomacular traction, and macular hole. With intravitreal TCA, there was a significant decrease in central foveal thickness at 3, 6, and 12 months, compared with baseline (P = 0.0171, 0.0401, and 0.0024, respectively). A significant gain in vision was noted at 1 month compared with baseline (P = 0.0169), but this was not sustained at 3, 6, and 12 months (P = 0.4862, 0.9098, and 0.4312, respectively). The addition of bevacizumab to TCA did not provide any additional benefit for central foveal thickness and visual acuity. Thirty-two eyes (82.1%) were started on prophylactic antiglaucoma drops 2 weeks after a TCA injection, and no eye needed laser or surgery to control intraocular pressure. Conclusion: Chronic CME after pars plana vitrectomy is recurrent and difficult to treat. Intravitreal TCA is effective in reducing CME, but there was only short-term visual acuity improvement even with continued reduction of central foveal thickness. Intraocular pressure did not significantly rise with the use of prophylactic antiglaucoma drops even with repeated injections.

ANALYSIS OF A CONFOCAL SCANNING LASER OPHTHALMOSCOPE NONCONTACT ULTRA-WIDE FIELD LENS SYSTEM IN RETINAL AND CHOROIDAL DISEASE.

Carl Zeiss was the first company to commercially introduce a fundus camera in 1926 with a 20-degrees field of view1. As technology evolved, 30-degrees became the standard field of view in ophthalmology, and now fundus cameras, which use up to 50–55 degrees fields of view are widely used in clinical practice. Imaging angles or views wider than 50-degrees have been referred to as “wide-field” or “wide-angle”1. Recently the term “ultra-wide field” has come to popularity although the exact definition and area of the retina imaged is not clearly defined. Confocal scanning laser ophthalmoscopy (cSLO) is an imaging technology that uses laser light to raster scan the retina, instead of a bright white flash used in standard fundus cameras, which provides better comfort to the patient. The reflected light is then captured through a small aperture (confocal pinhole) blocking the scattered light, giving a sharp, better quality and high contrast image2. This technology, coupled with a spectral-domain optical coherence tomography (SD-OCT) makes up the multi-modal imaging of the Spectralis HRA+ OCT (Heidelberg Engineering, Carlsbad, CA). It has a replaceable 30 × 30-degrees standard lens and a 55-degrees wide field lens. Recently, the company introduced a noncontact ultra-wide field (UWF) lens system that is capable of imaging from equator to equator and sufficient to image important details in the retinal periphery, such as vascular abnormalities anterior to the equator. This paper aimed to evaluate the quality and usability of Heidelberg Engineering’s recent addition of the noncontact ultra wide field lens system to image retinal and choroidal pathology, especially those in the mid and far periphery using different imaging modalities, namely, fundus autofluorescence (FAF), fluorescein angiography (FA), and indocyanine green angiography (ICGA).

The efficacy and safety of adalimumab in ocular inflammatory disease

License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php Orphan Drugs: Research and Reviews 2015:5 69–74 Orphan Drugs: Research and Reviews Dovepress