Vaidehi S. Dedania

Sustained Elevation Of Intraocular Pressure After Intravitreal Anti-vegf Agents: What Is the Evidence?

Purpose: To summarize the literature addressing sustained and delayed elevation of intraocular pressure (IOP) in patients with neovascular age-related macular degeneration being treated with intravitreal vascular endothelial growth factor (VEGF) inhibitors and to present possible mechanisms of effect. Methods: Analysis of current literature evaluating sustained and delayed elevation of IOP in patients receiving intravitreal anti-VEGF therapy for neovascular age-related macular degeneration. Results: Studies have demonstrated that patients undergoing treatment with intravitreal anti-VEGF agents may experience sustained and delayed elevation of IOP. The incidence of sustained elevation of IOP in patients with neovascular age-related macular degeneration varied from 3.45% to 11.6%, and few patients required surgical management to control IOP. Possible risk factors associated with sustained and delayed elevation of IOP include, but are not limited to, history of glaucoma, phakia, history of glucocorticoid use, and/or extended treatment duration. There are multiple theories explaining the pathogenesis of sustained elevation of IOP, including microparticle obstruction of the trabecular meshwork, intraocular inflammation, and transient elevation of IOP. Conclusion: Sustained and delayed elevation of IOP in patients undergoing treatment of neovascular age-related macular degeneration with intravitreal anti-VEGF agents is likely a multifactorial process. Further studies to prospectively investigate sustained elevation of IOP in large, randomized, controlled trials might lead to a better understanding of the long-term adverse events associated with intravitreal anti-VEGF therapy.

Pharmacogenomics Of Response To Anti-vegf Therapy In Exudative Age-related Macular Degeneration

Purpose: To determine whether there is an association between response to intravitreal anti-vascular endothelial growth factor agents and genotype in patients with neovascular age-related macular degeneration. Methods: Analysis of the current literature evaluating pharmacogenetics of treatment response in patients with neovascular age-related macular degeneration. Results: Studies have demonstrated associations between various genotypes and response to intravitreal anti-vascular endothelial growth factor agents. Lower-risk genotypes of the CFH, ARMS2, HTRA1, and VEGF-A genes may be associated with improved visual outcomes. Additionally, frequency of injections may be associated with certain genotypes. Conclusion: Genetic background may influence an individuals response to treatment of neovascular age-related macular degeneration. Further studies to investigate biologic pathways of neovascular age-related macular degeneration and gene products that are directly involved might lead to better understanding of contribution of various genes to treatment response.

Safety and Feasibility of Quantitative Multiplexed Cytokine Analysis From Office-Based Vitreous Aspiration.

Purpose The goals of this study were to evaluate the safety of office-based vitreous sampling, and determine the utility of these samples with multiplex cytokine analysis. Methods Vitreous samples were collected from office-based needle aspiration and the rate of adverse events during follow-up was reviewed. The vitreous cytokine concentrations in a subset of patients with diabetic macular edema (DME) were analyzed using a 42 plex-cytokine bead array. These results were compared with vitreous cytokine concentrations in proliferative diabetic retinopathy (PDR) and controls (macular hole, epiretinal membrane, symptomatic vitreous floaters) from pars plana vitrectomy. Results An adequate volume of vitreous fluid (100–200 μL) was obtained in 52 (88%) of 59 office-based sampling attempts. The average length of follow-up was 300 days (range, 42–926 days). There were no complications, including cataract, retinal tear or detachment, and endophthalmitis. Two patients (3%) had posterior vitreous detachments within 3 months. Vitreous cytokine concentrations were measured in 44 patients: 14 controls, 13 with DME, and 17 with PDR. The concentration of ADAM11, CXCL-10, IL-8, and PDGF-A were higher in PDR compared with controls and DME. The concentration of IL-6 was higher in PDR compared with controls, but not compared with DME. Conclusions Office-based vitreous aspiration is safe and yields high-quality samples for multiplex vitreous cytokine analysis. Significant elevations of vitreous cytokines were found in PDR compared with DME and controls, including the novel finding of elevated ADAM11. As such, office-based aspiration is a safe and effective means to identify vitreous factors associated with vitreoretinal disease.

Systemic safety of intravitreal anti-vascular endothelial growth factor agents in age-related macular degeneration.

Purpose of review The purpose of review is to summarize the literature addressing nonocular adverse events in patients with neovascular age-related macular degeneration treated with intravitreal vascular endothelial growth factor (VEGF) inhibitors and to present possible mechanisms of effect. Recent findings The incidence of overall nonocular serious adverse events varied from 0 to 39.3% and nonocular adverse events ranged from 0 to 86.9%. Few studies have reported a significant association between use of intravitreal anti-VEGF agents and overall incidence of adverse events, stroke, myocardial infarction, nonocular hemorrhage and death, with overall greater concern in patients treated with bevacizumab. Additionally, history of stroke or other arterial thromboembolic event may be a risk factor for future stroke in patients treated with intravitreal anti-VEGF agents. Theories explaining the mechanisms of increased risk of nonocular adverse events secondary to anti-VEGF agent use surround the necessity of VEGF for the normal functioning of the endothelium and the damage incurred with use of anti-VEGF agents. Summary Current data are insufficient to definitively conclude that intravitreal anti-VEGF agents are safe, although there is a trend toward an overall favorable systemic safety profile. Caution should be exerted in patients with a history of cardiovascular disease, as these patients may be at greater risk for nonocular serious adverse events.

Novel Classification System For Combined Hamartoma Of The Retina And Retinal Pigment Epithelium

Purpose: To develop an anatomical classification scheme for combined hamartoma of the retina and retinal pigment epithelium (RPE) and specify recommendations for follow-up interval. Methods: Retrospective review of patients with combined hamartoma of the retina and RPE examined during a 7-year period (2008–2015). The clinical presentation, fundus examination, and optical coherence tomography were analyzed. Results: Lesions were classified based on location, fundus features, and optical coherence tomography findings. Lesion location: macular/peripapillary—Zone 1; mid-periphery—Zone 2; and far periphery—Zone 3. Associated fundus findings: no retinal traction—Stage 1; retinal traction and/or retinoschisis—Stage 2; and retinal detachment—Stage 3. Optical coherence tomography findings: epiretinal component only—A; partial retinal involvement—B; and complete retinal and RPE involvement—C. Complete ophthalmologic evaluation is recommended at least every 6 months for patients younger than 12 years, with more frequent follow-up in patients with: lesions in the macula/peripapillary (Zone 1) or with retinal traction, retinoschisis, or retinal detachment (Stage 2 and 3). Surgical intervention is recommended in patients with vision loss secondary to macular traction or retinal detachment. Conclusion: A new clinical classification system is proposed for evaluating and managing patients with combined hamartoma of the retina and RPE. The zone and stage of combined hamartoma of the retina and RPE lesion will assist in determining follow-up interval and surgical intervention. Application of a uniform classification scheme will facilitate assessment and comparison of findings across different studies.

Endogenous endophthalmitis due to clinically vancomycin-resistant Staphylococcus aureus.

PURPOSE To report a case of clinically vancomycin-resistant Staphylococcus aureus endophthalmitis. METHODS This is an observational case report of a patient referred for decreased vision during an admission for methicillin-resistant S. aureus bacteremia. RESULTS A 48-year-old woman with methicillin-resistant S. aureus bacteremia presented with decreased vision in one eye. Best-corrected visual acuity at presentation was 20/25 in the right eye and hand motion in the left eye. Biomicroscopic examination revealed evidence of endophthalmitis in both eyes. After a period of deterioration despite treatment with intravenous and intravitreal vancomycin and intravitreal ceftazidime-20/200 in the right eye and light perception in the left eye, an alternative treatment regimen with intravenous daptomycin and intravitreal clindamycin and amikacin led to clinical improvement in both eyes, with quiescence of anterior chamber cell and vitritis. Best-corrected visual acuity at 3 weeks of follow-up had improved to 20/40 in the right eye and remained light perception in the left eye. CONCLUSION In cases of endogenous endophthalmitis secondary to methicillin-resistant S. aureus not responsive to intravenous and intravitreal vancomycin, particularly with borderline sensitivities, consideration to clinical resistance should be entertained.

CILIOCHOROIDAL EFFUSION and ACUTE MACULAR NEURORETINOPATHY ASSOCIATED with CERVICAL TRACTION THERAPY

Purpose: To report an unusual case of ciliochoroidal effusion and presumed acute macular neuroretinopathy associated with cervical traction therapy for the treatment of cervical spinal stenosis. Methods: Case report. Results: A 75-year-old man reported sudden onset of a wedge-shaped paracentral scotoma in the right eye. Fundus examination showed a ciliochoroidal effusion in the right eye. Optical coherence tomography revealed intraretinal fluid in both eyes without leakage on fluorescein angiography. B-scan ultrasonography and anterior segment ultrasound biomicroscopy of the right eye showed peripheral ciliochoroidal effusion. He had recently started intensive cervical traction therapy for the treatment of cervical spinal stenosis. There was spontaneous resolution of the choroidal effusion and intraretinal fluid after stopping cervical traction treatments. Optical coherence tomography imaging after resolution of the intraretinal fluid revealed thinning of the outer nuclear layer and attenuation of the ellipsoid and interdigitation zones corresponding to a persistent paracentral scotoma, consistent with acute macular neuroretinopathy. Conclusion: This is the first report of adverse ocular effects of cervical traction. We postulate that venous and arterial compromise during cervical traction therapy resulted in both ciliochoroidal effusion and a watershed infarct in the outer retina.

Peripheral Persistent Fetal Vasculature: A Report of Three Cases

The authors report three cases of persistent fetal vasculature (PFV) presenting with an atypical peripheral fibrovascular stalk. A 5-month-old with congenital exotropia with a vitreous hemorrhage in the right eye underwent vitrectomy, and a mid-peripheral vitreal vascular stalk was visualized within the area of hemorrhage. The second case is of an 8-year-old with two fetal vascular remnants in the right eye: (1) a stalk superotemporally extending from the pars plana to the mid-peripheral retina that was associated with a retinal break and (2) a focal lens opacity. The third case is a 12-year-old with a history of familial exudative vitreoretinopathy and peripapillary choroidal neovascular membrane found to have a peripheral vitreal stalk in the right eye. These cases demonstrate a rare form of PFV with primarily peripheral remnants. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e83-e88.].

Reliability of kinetic visual field testing in children with mutation-proven retinal dystrophies: Implications for therapeutic clinical trials

ABSTRACT Purpose: Kinetic visual field testing is used to monitor disease course in retinal dystrophy clinical care and treatment response in treatment trials, which are increasingly recruiting children. This study investigates Goldmann visual field (GVF) changes in young children with mutation-proven retinal dystrophies as they age and with progression of the retinal degeneration. Methods: Retrospective review of children ≤ 17 years old with a mutation-proven retinal dystrophy. Objective clinical disease activity was assessed by a retinal degeneration specialist masked to GVF results. Digital quantification of GVF area was performed. Results: Twenty-nine children (58 eyes), ages 5–16, were identified. GVF area increased with age despite progression in 20 children and clinical stability in nine children. Mean ± standard error increase in GVF area/year was 333 ± 130 mm2 (I4e, p = 0.012), 720 ± 155 mm2 (III4e, p < 0.001), and 759 ± 167 mm2 (IV4e, p < 0.001), with greater increases at earlier ages. Repeatability coefficients were 7381 mm2 (I4e), 9379 mm2 (III4e), and 10346 mm2 (IV4e), indicating a large variability. At 2.5 years after the baseline GVF the area increased ≥ 20%, the criterion for positive treatment outcome defined in recent published therapeutic trials, in 38% (I4e), 34% (III4e), and 33% (IV4e) of eyes. Conclusion: In a substantial proportion of children with mutation-proven retinal dystrophies, there is a significant increase in GVF area with age, particularly those < 12 years, despite progression or stability of disease. These findings suggest that change in GVF area in children with retinal dystrophies can be an unreliable measure of response to treatment and on which to base appropriate counseling about visual impairment.

Visual recovery after surgical repair of chronic macular detachment associated with peripheral retinoschisis

Purpose To report 2 cases of chronic macular detachment associated with peripheral retinoschisis in which surgical repair resulted in significant visual recovery. Observations A 44-year-old man and 60-year-old woman were evaluated for chronic macular detachment, with a duration of 5 years and 6 months, respectively. In each case, optical coherence tomography was used to establish a diagnosis of full-thickness macular detachment resulting from peripheral retinoschisis and to confirm or identify the pathogenic outer layer breaks. After surgical repair with pars plana vitrectomy, endolaser photocoagulation of outer layer breaks, and gas tamponade, both patients had significant improvement in vision. The best-corrected visual acuity improved from 20/50- to 20/20 at one year post-operatively in the first patient and from 20/1250 to 20/200 at 8 months post-operatively in the second. Conclusion and importance In cases of chronic schisis-detachment involving the macula, surgical intervention can sometimes result in unexpected levels of visual recovery.