Scott D. Schoenberger

Increased Prostaglandin E2 (PGE2) Levels in Proliferative Diabetic Retinopathy, and Correlation with VEGF and Inflammatory Cytokines

PURPOSE We determined vitreous levels of prostaglandin E2 (PGE(2)), VEGF, and 15 other cytokines in diabetic and nondiabetic patients undergoing vitrectomy. METHODS Of 26 eyes of 26 patients enrolled consecutively, 13 eyes underwent vitrectomy for complications related to proliferative diabetic retinopathy, and the other 13 for epiretinal membrane, macular hole, vitreous opacities, or dislocated intraocular lens. Undiluted vitreous samples were taken at the time of surgery and frozen immediately at -80°C, and later analyzed for PGE(2), VEGF, and 15 other cytokines. RESULTS PGE(2) levels were 53% higher in diabetic eyes. Mean ± standard deviation PGE(2) levels were 25.11 ± 11 pg/mL and 16.40 ± 7 pg/mL in diabetic and nondiabetic eyes, respectively (P < 0.03). Mean ± standard deviation VEGF levels were 2225 ± 3798 pg/mL and 66 ± 185 pg/mL in diabetic and nondiabetic eyes, respectively (P < 0.001). Other cytokines, including eotaxin-1, growth related oncogene (GRO), interleukin (IL)-6, IL-8, interferon-γ-inducible protein of 10 kDa (IP-10), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor alpha (TNF-α), and platelet-derived growth factor-AA, also were elevated significantly in diabetic eyes. A significant correlation was seen between PGE(2) levels and IP-10 and VEGF (P = 0.04). CONCLUSIONS PGE(2) levels are significantly higher in the vitreous of patients with complications from proliferative diabetic retinopathy, and correlate with IP-10 and VEGF. The results of our study suggest that PGE(2) may have a pathogenic role in diabetic retinopathy and implicates a potential therapeutic role for nonsteroidal anti-inflammatory drugs. (ClinicalTrials.gov number, NCT01609881.).

Topical Nonsteroidal Anti-inflammatory Drugs and Cataract Surgery: A Report by the American Academy of Ophthalmology

OBJECTIVE To review the available evidence on the effectiveness of prophylactic topical nonsteroidal anti-inflammatory drugs (NSAIDs) in preventing vision loss resulting from cystoid macular edema (CME) after cataract surgery. METHODS Literature searches of the PubMed and the Cochrane Library databases were last conducted on January 21, 2015, with no date restrictions. The searches retrieved 149 unique citations. The first author reviewed the abstracts of these articles and selected 27 articles of possible clinical relevance for full-text review. Of these 27 articles, 12 were deemed relevant to analyze in full. Two additional articles were identified from the reference list of the selected articles, and another article was identified from a national meeting. The panel methodologist assigned ratings of level of evidence to each of the selected citations. RESULTS Nonsteroidal anti-inflammatory drug therapy was effective in reducing CME detected by angiography or optical coherence tomography (OCT) and may increase the speed of visual recovery after surgery when compared directly with placebo or topical corticosteroid formulations with limited intraocular penetration. However, the use of NSAIDs did not alter long-term (≥3 months) visual outcomes. Furthermore, there was no evidence that the benefits observed with NSAID therapy could not be obtained similarly with equivalent dosing of a corticosteroid. The reported impression that there is a pharmacologic drug synergy from the use of both an NSAID and a corticosteroid is not supported by the literature. There is no uniform method of reporting CME in the literature, which prevents accurate assessment of its incidence and response to anti-inflammatory therapies. CONCLUSIONS Cystoid macular edema after cataract surgery has a tendency to resolve spontaneously. There is a lack of level I evidence that supports the long-term benefit of NSAID therapy to prevent vision loss from CME at 3 months or more after cataract surgery. Although dosing of NSAIDs before surgery may hasten the speed of visual recovery in the first several weeks after cataract surgery, there is no evidence that this practice affects long-term visual outcomes. Standardized reporting of CME based on OCT may allow for more uniform quantitation of its incidence and more reliable assessment of treatment outcomes.

Therapies for macular edema associated with central retinal vein occlusion: a report by the American Academy of Ophthalmology.

PURPOSE To review the available evidence regarding the safety and efficacy of therapies for the treatment of macular edema (ME) associated with central retinal vein occlusion (CRVO). METHODS A literature search of the PubMed database was last conducted in March 2014 with no date restrictions but limited to articles published in English. A literature search of the Cochrane Library was also conducted in March 2014 with no date restrictions and without a language limitation. The combined searches yielded 108 citations, of which 20 were deemed clinically relevant for the Ophthalmic Technology Assessment Committee Retina/Vitreous panel to review in full text. Three additional studies were also identified for panel review. The level of evidence of these selected studies was reviewed by the panel methodologist. RESULTS There were 7 citations representing 4 clinical trials that provided level I evidence supporting the use of anti-vascular endothelial growth factor (VEGF) pharmacotherapies for ME associated with CRVO, including intravitreal ranibizumab (2), aflibercept (3), and bevacizumab (2). There were 3 citations representing 2 studies with level I evidence for intravitreal corticosteroid injection with dexamethasone intravitreal implant (2 citations) or triamcinolone (1 citation), although cataract and glaucoma were observed in these studies. Level I evidence is available on the limited benefit of macular grid-pattern laser photocoagulation (1 citation). Eight other citations reviewed were rated as level II, and 4 citations were rated as level III. Long-term efficacy results (≥2 years of follow-up) are limited to intravitreal ranibizumab at this time, and few studies have evaluated combination therapy with anti-VEGF and corticosteroid versus monotherapy of either class of drug. CONCLUSIONS Level I evidence indicates that intravitreal anti-VEGF pharmacotherapy is safe and effective over 2 years for ME associated with CRVO and that delay in treatment is associated with worse visual outcomes. In addition, level I evidence demonstrates short-term efficacy of intravitreal corticosteroid but also an association with a higher frequency of adverse events.

Nonsteroidal Anti-Inflammatory Drugs for Retinal Disease

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used extensively in ophthalmology for pain and photophobia after photorefractive surgery and to reduce miosis, inflammation, and cystoid macular edema following cataract surgery. In recent years, the US Food and Drug Administration has approved new topical NSAIDs and previously approved NSAIDs have been reformulated. These changes may allow for greater drug penetration into the retina and thereby offer additional therapeutic advantages. For example, therapeutic effects on diabetic retinopathy and age-related macular degeneration may now be achievable. We provide an updated review on the scientific rationale and clinical use of NSAIDs for retinal disease.

Bilateral Multifocal Central Serous-Like Chorioretinopathy due to MEK Inhibition for Metastatic Cutaneous Melanoma

Newer chemotherapeutic agents target extracellular signaling, including the mitogen-activated protein kinase kinase (MEK) pathway. We present a case of a 54-year-old female who developed bilateral multifocal central serous-like chorioretinopathy shortly after starting MEK inhibition for metastatic cutaneous melanoma. There was a complete resolution of findings after drug stoppage. After resuming a lower dose of the MEK inhibitor, the findings recurred again but resolved after drug stoppage. Other etiologies were unlikely given the clinical course. The presumed mechanism involves toxicity to the retinal pigment epithelium, with breakdown of the blood-retinal barrier. Recognition of this side effect is important with this new class of chemotherapy.

Therapies for Macular Edema Associated with Central Retinal Vein Occlusion

PURPOSE To evaluate the available evidence on the ocular safety and efficacy of current therapeutic alternatives for the management of macular edema (ME) secondary to branch retinal vein occlusion (BRVO). METHODS Literature searches were last conducted on January 31, 2017, in PubMed with no date restrictions and limited to articles published in English, and in the Cochrane Database without language limitations. The searches yielded 321 citations, of which 109 were reviewed in full text and 27 were deemed appropriate for inclusion in this assessment. The panel methodologist assigned ratings to the selected studies according to the level of evidence. RESULTS Level I evidence was identified in 10 articles that addressed anti-vascular endothelial growth factor (VEGF) pharmacotherapies for ME, including intravitreal bevacizumab (5), aflibercept (2), and ranibizumab (4). Level I evidence was identified in 6 studies that examined intravitreal corticosteroids, including triamcinolone (4) and the dexamethasone implant (2). Level I evidence also was available for the role of macular grid laser photocoagulation (7) and scatter peripheral laser surgery (1). The inclusion of level II and level III studies was limited given the preponderance of level I studies. The number of studies on combination therapy is limited. CONCLUSIONS Current level I evidence suggests that intravitreal pharmacotherapy with anti-VEGF agents is effective and safe for ME secondary to BRVO. Prolonged delay in treatment is associated with less improvement in visual acuity (VA). Level I evidence also indicates that intravitreal corticosteroids are effective and safe for the management of ME associated with BRVO; however, corticosteroids are associated with increased potential ocular side effects (e.g., elevated intraocular pressure, cataracts). Laser photocoagulation remains a safe and effective therapy, but VA results lag behind the results for anti-VEGF therapies.

A novel mutation at the N-terminal domain of the TIMP3 gene in Sorsby fundus dystrophy.

Purpose: To report a novel mutation occurring in the N-terminal domain of the tissue inhibitor of metalloproteinase 3 (TIMP3) gene in Sorsby fundus dystrophy. Methods: Retrospective review of medical records of two patients who had clinical features consistent with Sorsby fundus dystrophy. Genetic testing confirmed a mutation in the TIMP3 gene in both patients. Results: Both patients had findings of drusenlike deposits, retinal pigment epithelial and photoreceptor atrophy, and bilateral, recurrent choroidal neovascularization. A strong family history of early onset macular degeneration was present in both. The patients developed choroidal neovascularization at the age of 45 and 48 years, and both had multiple recurrences in both eyes. Genetic testing in both patients confirmed a heterozygous nucleotide change of C113G, causing a Ser38Cys change in Exon 1 of the N-terminal domain of the TIMP3 gene. Conclusion: All previously reported mutations in Sorsby fundus dystrophy occur at Exon 5 in the C-terminal domain. We report 2 patients with novel mutations in Exon 1 of the N-terminal domain. Although the mutation occurs at a different location on the TIMP3 gene, the clinical features are similar to other reported patients with Sorsby fundus dystrophy. This finding assists in understanding the pathogenesis of this disorder.

Tropheryma whipplei Crystalline Keratopathy: Report of a Case and Updated Review of the Literature.

Purpose. To report a case of Tropheryma whipplei infection with crystalline keratopathy and review the recent literature on the presentation, diagnosis, and management of Whipples disease. Methods. Detailed case presentation and extensive literature search of Pubmed for all years through February 2012 using the following search terms: Whipples disease, Tropheryma whipplei, corneal deposits, crystalline keratopathy, and uveitis. Relevant articles were retrieved and analyzed. English abstracts were used for non-English articles. Cross-referencing was employed and reference lists from selected articles were used to identify additional pertinent articles. Results. Diagnosis of Whipples disease remains challenging and untreated infection can result in mortality. Ocular signs and symptoms are usually nonspecific, but several independent cases have reported the presence of intraocular crystals or crystalline-like deposits. Conclusions. The presence of intraocular crystals or crystalline-like deposits may be an identifying feature of ocular Whipples disease.

Acute macular neuroretinopathy: an atypical case.

PURPOSE The purpose of this report is to describe extensive acute macular neuroretinopathy lesions with atypical features. METHODS Retrospective case report. RESULTS A patient developed acute macular neuroretinopathy in the setting of multiple previously described associations including a flu-like illness, sympathomimetic exposure, overdose of norepinephrine reuptake inhibitors, anemia, thrombocytopenia, and hypotensive shock. The fundus lesions superficially resembled retinal hemorrhages in color and fluorescein angiography pattern. The lesions could be detected on autofluorescence and infrared imaging. Optical coherence tomography revealed outer plexiform layer opacification and photoreceptor abnormalities. CONCLUSION This case suggests a compounding effect of factors associated with acute macular neuroretinopathy, possible exacerbating insults and outer plexiform layer abnormalities that may correlate with the temporal course of this condition.

Paraneoplastic Optic Neuropathy From Cutaneous Melanoma Detected by Positron Emission Tomographic and Computed Tomographic Scanning

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