Roberto Gallego-Pinazo

Anterior chamber migration of dexametasone intravitreal implant (Ozurdex

Dear Editor, Ozurdex® (Allergan Inc., Irvine, CA, USA) is an intravitreal implant containing the dexamethasone. It uses NOVADUR® drug delivery technology, in which a biodegradable material is combined with the active drug dexamethasone to form a small rod-shaped implant of 0.46 mm in diameter and 6 mm in length. Inside the eye, the implant is progressively dissolved in the vitreous gel, as it slowly releases dexamethasone (0.7 mg). This biodegradable device is indicated for the treatment of macular edema following branch or central retinal vein occlusions. In large clinical trials, Ozurdex® has also proved effective in the treatment of posterior non-infectious uveitis, and diabetic and macular edema to and pseudophakic macular edema [1, 2]. Herein we report the case of a 68-year-old male diagnosed with macular edema following branch retinal vein occlusion in his left eye. Visual acuity was 0.6 logMAR. The patient had undergone cataract surgery years before, with intraoperative violation of the lens posterior capsula, anterior vitrectomy assisted with triamcinolone and iris-claw intraocular lens implantation. An intravitreous injection of Ozurdex® (Allergan Inc., Irvine, CA, USA) was performed without remarkable complications. Three weeks later, the patient attended our emergency department complaining of blurred vision in his left eye. Slit-lamp examination revealed the presence of diffuse corneal edema, and anterior migration of the implant (Fig. 1). The intraocular pressure measured 18 mmHg. The implant was surgically removed from the anterior chamber 48 hours later. However, corneal edema did not resolve, and the patient finally underwent corneal transplantation. The anterior chamber transit has been previously described for triamcinolone acetonide, resulting in pseudohypopion [3, 4]. Probably due to a similar mechanism, the dexamethasone implant may also migrate into the anterior chamber, with secondary corneal descompensation due to the contact of the implant with the endothelium. This may be more frequent in pseudophakic cases with Nd-YAG capsulotomy, or posterior capsule violation during phacoemulsification. Nevertheless, pseudohypopion after intravitreal triamcinolone injection has been described in both phakic or pseudophakic patients with posterior capsule integrity, it being presupposed then that the zonula is not complete or that the crystals are capable of crossing through it [3, 4]. In this particular case, the lack of anterior hyaloid may facilitate the penetration of Ozurdex into the anterior chamber too. In our opinion, the state of anterior hyaloid can be assessed by slit-lamp examination only. However, ecography could be useful in cases of uncertain anterior hyaloid status. The authors certify that they have not been published or are being considered for publication elsewhere. The authors also transfer property rights (copyright) of this work to Graefe’s Archive for Clinical and Experimental Opthalmology. D. Pardo-Lopez : E. Frances-Munoz :R. Gallego-Pinazo : M. Diaz-Llopis Department of Ophthalmology, University and Polytechnic Hospital La Fe, Valencia, Spain

Evaluation of presumptive biomarkers of oxidative stress, immune response and apoptosis in primary open-angle glaucoma.

There is growing interest on the correlation among oxidative stress, inflammation, apoptosis and primary open-angle glaucoma initiation and progression. Reactive oxygen species are formed in the eyes following a wide variety of stressors, and are largely implicated in glaucoma pathogenesis. Immune-inflammatory response mediators have recently become a target of ophthalmologic concern, including glaucoma. Much attention has been derived to the role of specific pro and anti-apoptotic molecules in glaucoma. This article reviews the early evidence suggesting that reactive oxygen species, immune inflammatory response mediators, and apoptogenic molecules are engaged in glaucoma disease. Moreover, further research concerning the functions, effectors and signaling pathways of the above molecules and their interactions, may lead to specifically develop targeted screening tools based on presumptive biomarkers and surrogate endpoints against primary open-angle glaucoma progression and blindness.

Acute Zonal Occult Outer Retinopathy: A Classification Based on Multimodal Imaging

IMPORTANCE We describe the multimodal imaging in a group of patients showing a distinct clinical entity that best represents acute zonal occult outer retinopathy (AZOOR). OBJECTIVE To propose a classification of AZOOR based on clinical fundus and multimodal imaging. DESIGN, SETTING AND PARTICIPANTS A retrospective review of patients diagnosed as having AZOOR at 2 centers. After reviewing more than 400 cases diagnosed or referred to us as AZOOR or AZOOR complex, we assembled 30 cases that fit our current definition; (48 eyes) with a median age at diagnosis of 47 years (age range, 17-86 years) and a mean follow-up period of 39 months. Twenty patients were female. Eighteen patients had initially been seen with bilateral lesions, mostly asymmetric (4 cases were symmetric). Most patients had no remarkable medical or ocular history. The median visual acuity at the time of presentation was 20/25 (range, 20/20 to 20/400). MAIN OUTCOMES AND MEASURES Multimodal imaging, including fundus photography, fluorescein and indocyanine green angiography, fundus autofluorescence imaging, and corresponding eye-tracked spectral-domain coherence tomography imaging. RESULTS Each patient was initially seen with visual symptoms of photopsia and scotoma, and most had a detectable lesion in the fundus evident clinically or detected on multimodal imaging. The clinical appearance of the AZOOR lesions varied depending on their duration and location, but some features were characteristic, including a demarcating line of the progression at the level of the outer retina and a trizonal pattern of sequential involvement of the outer retina, retinal pigment epithelium, and choroid, as well as frequent zonal progression. Advanced cases of AZOOR demonstrated disruption of the inner and outer retina and severe damage or loss of the retinal pigment epithelium and the choroid. CONCLUSIONS AND RELEVANCE A specific definition of AZOOR based on multimodal imaging is proposed to help physicians distinguish it from other diseases of the posterior fundus, including white spot syndromes and autoimmune, hereditary, paraneoplastic, toxic, and other inflammatory retinopathies.

Oxidative stress and its downstream signaling in aging eyes

Background Oxidative stress (OS) and its biomarkers are the biochemical end point of the imbalance between reactive oxygen species (ROS) production and the ability of the antioxidant (AOX) biological systems to fight against oxidative injury. Objective We reviewed the role of OS and its downstream signaling in aging eyes. Methods A search of the literature and current knowledge on the physiological and pathological mechanisms of OS were revisited in relation to the eyes and the aging process. Most prevalent ocular diseases have been analyzed herein in relation to OS and nutraceutic supplements, such as dry-eye disorders, glaucoma, age-related macular degeneration, and diabetic retinopathy. Results Clinical, biochemical, and molecular data from anterior and posterior eye segment diseases point to OS as the common pathogenic mechanism in the majority of these ocular disorders, many of which are pathologies causing visual impairment, blindness, and subsequent loss of life quality. Studies with nutraceutic supplements in aging eye-related pathologies have also been reviewed. Conclusion OS, nutritional status, and nutraceutic supplements have to be considered within the standards of care of older ophthalmologic patients. OS biomarkers and surrogate end points may help in managing the aging population with ocular diseases.

Smoking and Age-Related Macular Degeneration: Review and Update

Age-related macular degeneration (AMD) is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health.

Update on the principles and novel local and systemic therapies for the treatment of non-infectious uveitis.

Ocular inflammatory disorders constitute a sight-threatening group of diseases that might be managed according to their severity. Their treatment guidelines experience constant changes with new agents that improve the results obtained with former drugs. Nowadays we can make use of a five step protocol in which topical, periocular and systemic corticosteroids remain as the main therapy for non-infectious uveitis. In addition, immunosuppresive drugs can be added in order to enhance the anti-inflammatory effects and to play the role of corticosteroid-sparing agents. These can be organized in four other steps: cyclosporine and methotrexate in a second one; azathioprine, mycophenolate and tacrolimus in a third step; biological anti-TNF drugs in fourth position; and a last one with cyclophosphamide and chlorambucil. In the present review we go through the main characteristics and complications of all these treatments and make a rational of this five-step treatment protocol for non-infectious posterior uveitis.

Long-Term Visual Outcomes for a Treat and Extend Anti-Vascular Endothelial Growth Factor Regimen in Eyes with Neovascular Age-Related Macular Degeneration

With the advent of anti-vascular endothelial growth factor (VEGF) therapy, clinicians are now focused on various treatment strategies to better control neovascular age-related macular degeneration (NVAMD), a leading cause of irreversible blindness. Herein, we retrospectively reviewed consecutive patients with treatment-naïve NVAMD initially classified based on fluorescein angiography (FA) alone or with an anatomic classification utilizing both FA and optical coherence tomography (OCT) and correlated long-term visual outcomes of these patients treated with an anti-VEGF Treat-and-Extend Regimen (TER) with baseline characteristics including neovascular phenotype. Overall, 185 patients (210 eyes) were followed over an average of 3.5 years (range 1–6.6) with a retention rate of 62.9%, and visual acuity significantly improved with a TER that required a mean number of 8.3 (±1.6) (± standard deviation) intravitreal anti-VEGF injections/year (range 4–13). The number of injections and the anatomic classification were independent predictors of visual acuity at 6 months, 1, 2, 3 and 4 years. Patients with Type 1 neovascularization had better visual outcomes and received more injections than the other neovascular subtypes. There were no serious adverse events. A TER provided sustained long-term visual gains. Eyes with Type 1 neovascularization had better visual outcomes than those with other neovascular subtypes.

Residual internal limiting membrane after epiretinal membrane peeling: results of the Pan-American Collaborative Retina Study Group.

Purpose: To determine the degree of residual internal limiting membrane (ILM) after idiopathic epiretinal membrane (ERM) peeling and the usefulness of staining with brilliant blue G. Methods: A prospective, multicenter, observational study of 98 eyes undergoing pars plana vitrectomy and membrane peeling for idiopathic ERM. All eyes underwent core vitrectomy (20, 23, or 25 gauge) followed by intravitreal triamcinolone to verify that the posterior hyaloid had been removed. Brilliant blue G (0.2 mL of 0.25 mg/mL) was injected into the vitreous cavity and washed out immediately. The ERM was peeled and then the surgeon observed and recorded the characteristics of the underlying ILM. The posterior pole was restained with brilliant blue G (0.2 mL of 0.25 mg/mL), and the same observations on the characteristics of the ILM were recorded. Peeling of the remaining ILM was performed. The main outcome measured was the status of the ILM after ERM peel. Secondary outcomes included best-corrected visual acuity and central macular thickness at 6 months postoperatively. Results: After ERM peel, all of the eyes had residual ILM. In 74 eyes, the ILM was present and damaged, whereas in 24 eyes, the ILM was present and undamaged. In 37 eyes, the operating surgeon was unable to determine the status of the ILM before brilliant blue G staining. At 6 months, the logarithm of the minimum angle of resolution best-corrected visual acuity improved from 0.75 ± 0.39 at baseline to 0.31 ± 0.26 (P < 0.0001). The central macular thickness also improved from 460 ± 91 &mgr;m at baseline to 297 ± 102 &mgr;m (P < 0.003). Conclusion: Internal limiting membrane is frequently still present after ERM peeling. Staining with brilliant blue G facilitates its identification.

Correlation between neovascular lesion type and clinical characteristics of nonneovascular fellow eyes in patients with unilateral, neovascular age-related macular degeneration.

Purpose: To investigate the association between the type of neovascularization (NV) and the clinical characteristics of nonneovascular fellow eyes in patients with unilateral, neovascular age-related macular degeneration. Methods: Eighty-three patients with treatment-naive, unilateral, neovascular age-related macular degeneration were retrospectively analyzed. Neovascular lesions were classified using both fluorescein angiography and optical coherence tomography as Type 1 (subretinal pigment epithelium), 2 (subretinal), 3 (intraretinal), or mixed NV. The associations between NV lesion type and baseline clinical and imaging characteristics of the fellow eye, including central geographic atrophy, noncentral geographic atrophy, pigmentary changes, soft drusen, cuticular drusen, reticular pseudodrusen, and subfoveal choroidal thickness, were examined. Subfoveal choroidal thickness was defined as thin if thickness was <120 &mgr;m. Results: In the fellow eyes of patients with treatment-naive, unilateral, neovascular age-related macular degeneration, Type 3 NV had an increased adjusted odds ratio of reticular pseudodrusen (15.361, P < 0.001) and thin subfoveal choroidal thickness (21.537, P < 0.001) as well as a tendency toward an increased adjusted odds ratio of central geographic atrophy (4.775, P = 0.028). Fellow eyes of patients with Type 1 NV showed a decreased adjusted odds ratio of reticular pseudodrusen (0.233, P = 0.007) and thin subfoveal choroidal thickness (0.080, P = 0.005). Conclusion: In patients with unilateral, neovascular age-related macular degeneration, certain nonneovascular features of the fellow eye correlate with the NV lesion composition based on type, as anatomically classified utilizing both fluorescein angiography and optical coherence tomography. Patients with Type 3 NV were more likely to have reticular pseudodrusen and/or thin subfoveal choroidal thickness in the fellow eye compared with those with Type 1 NV. Patients with Type 3 NV also showed a trend toward increased central geographic atrophy in the fellow eye.

Baseline Predictors for Good Versus Poor Visual Outcomes in the Treatment of Neovascular Age-Related Macular Degeneration With Intravitreal Anti-VEGF Therapy.

PURPOSE To examine the baseline factors associated with good (20/60 or better) versus poor (20/200 or worse) visual outcomes in eyes with treatment-naïve neovascular age-related macular degeneration (AMD) receiving intravitreal antivascular endothelial growth factor (VEGF) on a treat-and-extend regimen (TER). METHODS An observational, retrospective series of patients managed with a TER, identified as having either good or poor visual outcomes, was examined. A multivariate regression analysis of baseline characteristics identified factors associated with good and poor vision at 2, 3, and 4 years. Neovascular subtypes were identified using fluorescein angiography (FA) alone and the anatomic classification system with FA and optical coherence tomography (OCT). RESULTS One hundred thirty-eight patients (154 eyes) fit the inclusion criteria at 2 years, 106 patients (113 eyes) at 3 years, and 72 patients (74 eyes) at 4 years. In the multivariate analysis, type 1 lesions, according to anatomic classification, had better vision at 24 months (95% CI: [3.1, 82.7], P = 0.01), 36 months (95% CI: [1.97, 24.17], P = 0.003), and 48 months (95% CI: [2.01, 65.47], P = 0.006). Clopidogrel use was associated with poor vision at 24 months (95% CI: [0.03, 0.68], P = 0.013). Vision at 3 months was the best predictor of vision at year 4 (β = -4.277, P = 0.002). CONCLUSIONS Eyes with neovascular AMD managed with a TER of anti-VEGF therapy having type 1 neovascularization at baseline were more likely to maintain good vision over 4 years, whereas clopidogrel use predicted poor vision at 2 years. Vision at 3 months was the best predictor for favorable long-term vision.