CATASTROPHIC, BILATERAL RETINAL VASCULAR OCCLUSION AFTER INTRAVITREAL BEVACIZUMAB INJECTION.

PURPOSE: To describe two cases of catastrophic, bilateral retinal vascular occlusion after intravitreal (IVT) bevacizumab injection. METHODS: Case series. Main outcome measures included clinical and fluorescein angiography findings. RESULTS: Case 1-A 65-year-old woman with calcinosis, Raynaud phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasis syndrome developed acute, severe, bilateral visual loss 2 weeks after bilateral IVT bevacizumab injection for proliferative diabetic retinopathy. Examination and fluorescein angiography revealed moderate anterior chamber inflammation, bilateral perivascular retinal hemorrhages, and near total retinal vascular occlusion. Extensive testing revealed moderately elevated anti-B2 glycoprotein (antiphospholipid) antibodies. Case 2-An 85-year-old man with polymyalgia rheumatica and left eye exudative age-related macular degeneration experienced severe, bilateral, sequential visual loss in the left eye and then right eye approximately 3 weeks after IVT bevacizumab left eye injection. Examination revealed bilateral panuveitis, diffuse perivascular exudates, and intraretinal hemorrhages. Fluorescein angiography showed diffuse venous leakage. Extensive testing revealed an elevated antinuclear antibody and mildly elevated anticardiolipin antibody. CONCLUSION: Patients with underlying retinal vascular vulnerabilities may be at increased risk of catastrophic, bilateral retinal vascular occlusion after treatment with IVT bevacizumab. The moderate-to-severe intraocular inflammation in both cases and the contralateral involvement after unilateral IVT injection in Case 2 suggest a possible delayed immune-mediated mechanism.

A 27-YEAR-OLD FEMALE WITH MILD BLURRY VISION AND PROLONGED LIGHT ADJUSTMENT IN THE MORNING.

PURPOSE: The following case report highlights a rare presentation of chronic myeloid leukemia-associated hyper-viscosity syndrome and provides a brief review of expected findings and treatment outcomes. METHODS: An otherwise healthy 27-year-old woman presented to the ophthalmology clinic with mild bilateral blurriness (20/20 in both eyes) and prolonged light adaption in the morning for several months. Examination demonstrated severe bilateral venous stasis, white-centered hemorrhages, intraretinal hemorrhage, and peripheral ischemia with diffuse leakage. RESULTS: Same-day CBC demonstrated a leukocytosis of >600,000. Subsequent bone marrow biopsy confirmed the 9,22 translocation (Philadelphia chromosome). On further examination, the patient had an enlarged cardiac silhouette, cytopenia, and splenomegaly past the umbilicus, consistent with a severe and life-threatening leukostasis. CONCLUSION: Ocular involvement can occur in acute and chronic leukemia. Five to ten percentage of patients present to an eye physician first, without a known diagnosis. Prompt systemic treatment can result in near-complete reversal of any intraocular injury in most mild-to-moderate cases, as was the case here.

Suprachoroidal CLS-TA for non-infectious uveitis: an open-label, safety trial (AZALEA).

PURPOSE: To evaluate local and systemic safety of suprachoroidal (SC) triamcinolone acetonide injectable suspension (CLS-TA) injections in subjects with non-infectious uveitis (NIU). DESIGN: Open-label, prospective multicentre safety study. PARTICIPANTS: Thirty-eight subjects with NIU, with and without macular oedema (MO). METHODS: Treatment consisted of two suprachoroidal injections of CLS-TA 4 mg, 12 weeks apart. Best-corrected visual acuity (BCVA), adverse event (AE) assessment, ophthalmic examinations and optical coherence tomography (OCT) were conducted every 4 weeks for 24 weeks. Blood samples were analysed for plasma triamcinolone acetonide (TA) concentrations. MAIN OUTCOME MEASURES: The main outcome measure was frequency of AEs. Other endpoints included plasma TA concentrations, change in signs of inflammation, BCVA and retinal central subfield thickness (CST). RESULTS: Based on a CST of >300 µm, 20 out of 38 subjects had MO at baseline. Mean intraocular pressure (IOP) was 13.3 mm Hg at baseline and 15.2 mm Hg at week 24 in the study eye. A total of six (15.8%) subjects had an IOP rise >10 mm Hg compared with baseline, in the study eye, and two (5.3%) subjects had IOP >30 mm Hg (maximum 34 mm Hg at week 8 and 38 mm Hg at week 20). Cataract formation AEs were reported in four study eyes; one of which was deemed treatment-related. No serious ocular AEs in the study eye occurred in the study. Quantifiable post-injection TA plasma concentration was <1 ng/mL. Efficacy parameters showed improvement over the 24-week study period. CONCLUSIONS: Suprachoroidally administered CLS-TA was safe and well tolerated over the 24-week, open-label study in NIU subjects with and without MO.

Choroidal nonperfusion on optical coherence tomography angiography in a case of unilateral posterior segment ocular sarcoidosis misdiagnosed as MEWDS.

PURPOSE: To report a case of presumed ocular sarcoidosis initially presenting with features of multiple evanescent white dot syndrome (MEWDS) with atypical optical coherence tomography angiography (OCTA) findings. OBSERVATIONS: A 23 year-old woman presented with a unilateral central scotoma, photophobia, and decreased visual acuity after a viral illness. Examination of the right eye revealed multiple round white macular spots and stippled granularity at the fovea. Multimodal imaging with fluorescein angiography (FA), indocyanine green angiography (ICG), fundus autofluorescence (FAF), and optical coherence tomography (OCT) was consistent with a diagnosis of MEWDS. However, OCTA demonstrated choriocapillaris (CC) flow deficits, which is not typical for MEWDS. The clinical course was initially consistent with MEWDS, with spontaneous recovery of symptoms over ensuing months. The patient presented five months later with floaters and a central scotoma. Examination showed panuveitis, and systemic evaluation revealed an elevated angiotensin converting enzyme (ACE) and hilar lymphadenopathy on chest x-ray consistent with presumed sarcoidosis. CONCLUSIONS AND IMPORTANCE: A case of MEWDS atypically demonstrated CC flow deficits on OCTA and subsequently presented as uveitis secondary to presumed sarcoidosis. Atypical features in MEWDS may be a sign of another disorder masquerading early on as MEWDS and ought to prompt further investigation.

Bilateral acute simultaneous onset anterior uveitis presumed secondary to erlotinib: A report of two cases.

PURPOSE: To report two new cases of presumed erlotinib-associated bilateral acute simultaneous-onset anterior uveitis effectively treated with topical steroids. OBSERVATIONS: Two patients were referred to the uveitis clinic with bilateral acute simultaneous onset, anterior uveitis six weeks after starting the chemotherapeutic agent erlotinib. Frequent topical steroid were started and the inflammation responded swiftly and completely. CONCLUSIONS AND IMPORTANCE: Bilateral acute simultaneous onset anterior uveitis is a potential side effect associated with erlotinib use that has not been well described. Physicians should be aware of this potential association in patients with recent treatment with erlotinib who complain of blurred vision, photophobia, or redness of the eyes. In some cases, the inflammation responds well to topical therapy and medication can be continued.

Fundus Autofluorescence Findings in Eyes With Birdshot Chorioretinitis.

Purpose: The purpose of this study was to describe fundus autofluorescence (FAF) findings in eyes with birdshot chorioretinitis (BSCR) and to compare findings to demographic, medical, and clinical characteristics. Methods: In this multicenter, prospective, cross-sectional study, 172 eyes (86 patients) with BSCR were investigated. Participants underwent a standardized evaluation including collection of demographic data, ophthalmic and treatment history, and ophthalmologic examination. Using a standardized protocol, hypo- and hyperautofluorescence in macular and extramacular regions and specific patterns of abnormal FAF could be scored for 167 eyes. Images were scored by two independent, masked graders. Measures of visual function included best-corrected visual acuity (BCVA), contrast sensitivity (CS), color vision, and Humphrey visual field mean deviation (HVF-MD). Results: Any abnormal FAF finding was observed in 132 eyes (79.0%); macular abnormalities were observed in 84 eyes (49.1%). The most common findings were peripapillary confluent hypoautofluorescence (122 eyes [73.1%]); extramacular granular hypoautofluorescence (100 eyes [59.9%]); and macular granular hypoautofluorescence (67 eyes [40.1%]). Confluent hypoautofluorescence was related to longer median disease duration (8.7 years) than granular hypoautofluorescence (7.9 years) or hyperautofluorescence (5.6 years). Macular confluent hypoautofluorescence was associated with BCVA ≤20/25 (odds ratio [OR] = 7.83, P = 0.007), BCVA ≤20/50 (OR = 4.94, P = 0.002), and abnormal CS (OR = 4.56, P = 0.009). Presence of macular or extramacular hypoautofluorescence was related to HVF-MD ≤-3 dB (OR = 2.43, P = 0.01 and OR = 2.89, P = 0.003, respectively). Conclusions: In this large cohort, various FAF abnormalities were found, indicating that disorders of the retinal pigment epithelium are features of BSCR. Abnormal FAF is a marker of visual dysfunction in the disease.

Utility of Leflunomide in the Treatment of Drug Resistant Cytomegalovirus Retinitis.

PURPOSE: To describe leflunomide use in the treatment of drug resistant cytomegalovirus retinitis. Leflunomide has been shown to be effective in the treatment of systemic CMV viremia. METHODS: Retrospective chart review of patients with CMV retinitis treated with leflunomide. RESULTS: Two HIV-negative organ transplant recipients with UL 97 mutation resistant-genotype CMV were identified. Patient 1 developed CMV viremia post-kidney transplant and subsequently bilateral CMV retinitis. Retinitis progressed, despite intravitreal injection of ganciclovir and foscarnet, and IV foscarnet and oral valganciclovir. Retinitis control was achieved with the addition of oral leflunomide. Disease remained inactive for 22 months. Patient 2 developed CMV retinitis after lung transplant. Disease progressed despite intravitreal foscarnet injections and oral valganciclovir. Control of retinitis was achieved with addition of oral leflunomide, allowing cessation of intravitreal therapy. Disease remained inactive until his death. CONCLUSIONS: Leflunomide may be considered as a treatment option for resistant CMV retinitis.

TARANTULA HAIR ASSOCIATED PANUVEITIS TREATED WITH SUSTAINED-RELEASE INTRAVITREAL DEXAMETHASONE IMPLANT.

PURPOSE: To report a case of tarantula hair-induced panuveitis treated with sustained-release intravitreal dexamethasone implant and followed by sequential spectral domain optical coherence tomography imaging. METHODS: Findings on clinical examination, anterior segment optical coherence tomography, corneal in vivo confocal microscopy, color fundus photos, fluorescein angiography, and retinal spectral domain optical coherence tomography are presented. Sequential optical coherence tomography images demonstrated the course of the chorioretinal lesions before and after sustained-release intravitreal dexamethasone implant. RESULTS: A 19-year-old female presented with localized temporal episcleritis and scleritis that incompletely resolved despite multiple courses of topical and oral corticosteroids. She subsequently developed focal vitritis and chorioretinitis, and was found to have tarantula hair-induced panuveitis. Anterior segment optical coherence tomography and in vivo confocal microscopy confirmed the presence of tarantula hairs embedded in the anterior corneal stroma. There was only transient improvement with posterior sub-Tenon's Kenalog injection. After treatment with sustained-release intravitreal dexamethasone implant, her symptoms improved and the chorioretinal lesions became inactive. Sequential spectral domain optical coherence tomography images revealed hyperreflective inner retina lesions that progressed to involve the outer retina, and then flattened to near resolution after therapy. CONCLUSION: This is the first case showing positive clinical outcomes supported by sequential retinal spectral domain optical coherence tomography using a sustained-release intravitreal dexamethasone implant to treat ophthalmia nodosa-induced by tarantula hairs.

Choroidal Findings in Eyes With Birdshot Chorioretinitis Using Enhanced-Depth Optical Coherence Tomography.

PURPOSE: The purposes of this study were to describe choroidal findings observed using optical coherence tomography with enhanced depth imaging (EDI-OCT) in eyes with birdshot chorioretinitis (BSCR) and to test the hypothesis that these findings are related to participant demographics, clinical characteristics, and treatment. METHODS: In a multicenter, cross-sectional study, 172 eyes of 86 individuals with BSCR underwent a standardized clinical evaluation, including defined protocols for EDI-OCT imaging, with macular and peripapillary volume scans. Choroidal findings were compared to demographic information, ophthalmic examination findings, and treatment history, using logistic regression models. EDI-OCT images were evaluated by two independent, masked graders. RESULTS: Median age was 56 years old; 54 participants (62.8%) were female. One or more choroidal lesions (a predefined hyporeflective zone) were identified in 105 eyes (63.6%). Median choroidal thickness was 293 µm. Choroidal lesions were associated with longer disease durations (odds ratio [OR]: 1.08; P = 0.03), increased vitreous haze (>0.5+; OR: 4.43; P = 0.02), presence of macular edema (OR: 3.00; P = 0.02), and thick choroids (OR: 3.89; P = 0.001). Use of immunomodulatory therapy was associated with lower risk of thin choroids (lower 25th percentile, OR: 0.17; P = 0.001) or thick choroids (upper 25th percentile, OR: 0.22; P = 0.002). At least some choroidal lesions did not have corresponding, clinically apparent "birdshot lesions" on fundus examination. CONCLUSIONS: Choroidal abnormalities identified by EDI-OCT imaging are common in the macular and peripapillary regions of eyes with BSCR. Choroidal lesions were associated with clinical signs of inflammation, suggesting that they represent foci of disease activity. EDI-OCT may provide useful information about disease mechanisms and response to treatment in future, longitudinal studies of BSCR.

A new OCT finding in tuberculous serpiginous-like choroidopathy.

PURPOSE: To present a case of tubercular serpiginous-like choroiditis (SLC) with previously unreported choroidal findings on enhanced depth imaging OCT (EDI-OCT). DESIGN: Case report. METHODS: A 60-year-old female presented with decreased vision. Serpiginous choroidopathy was diagnosed. Laboratory workup revealed an infectious etiology. EDI-OCT revealed previously unreported choroidal findings. RESULTS: Laboratory workup revealed nonreactive Treponema pallidum antibodies and positive QuantiFERON Gold. CT chest showed scars of prior granulomatous disease. OCT with EDI of active lesions demonstrated infiltration of the choroid, elevation of the RPE-Bruch's membrane complex and focal increase of choroidal thickness. CONCLUSIONS: Choroidal infiltration with elevation of the RPE was demonstrated on EDI-OCT in active areas of tuberculous serpiginous-like choroiditis in this patient. This finding has not been described in imaging of patients with noninfectious serpiginous choroidopathy and may be a useful tool to differentiate serpiginous choroidopathy (SC) from serpiginous-like choroiditis (SLC). EDI-OCT may provide characterization of choroidal involvement.

Sarcoidosis: sex-dependent variations in presentation and management.

Sarcoidosis is an inflammatory disease with a wide range of clinical presentations. The manifestations and prognosis in sarcoidosis are dependent upon not only organ involvement but also age and sex. The purpose of this review is to describe the systemic and ocular manifestations of sarcoidosis with a specific focus on sex-dependent difference in presentation and management. Sarcoidosis is more common in women, particularly in patients who present after age of 50 years. Women with sarcoidosis are more likely to develop cystoid macular edema and the mortality rate is higher than that of men.

TNF inhibition for ophthalmic indications: current status and outlook.

BACKGROUND: Tumor necrosis factors (TNF) are a group of cytokines that play a role in systemic inflammation, stimulating the acute phase reaction. They are involved in systemic rheumatologic conditions such as rheumatoid arthritis and juvenile idiopathic arthritis, as well as ocular inflammatory conditions in the uveitis spectrum. Several drugs were developed to inhibit the action of TNF, thereby reducing inflammation. The three most commonly used TNF inhibitors in the US are etanercept, infliximab, and adalimumab. Newer drugs include certolizumab and golimumab. In this review, we discuss the differences in the mechanism of action, route of administration, indication, and efficacy of TNF inhibitors used in the treatment of ocular inflammation. METHODS: A review of the literature in the PubMed, MEDLINE, and Cochrane databases was conducted to identify clinical trials, comparative studies, case series, and case reports describing the use of tumor necrosis factor inhibitors in uveitis therapy. The search was limited to primary reports published in English with human subjects from 1990 to the present, yielding 5,238 manuscripts. In addition, referenced articles from the initial searches were hand searched to identify additional relevant reports. After title and abstract selection, duplicate elimination, and manual search, 69 papers were selected for analysis. Exclusion criteria included review articles and case reports on the efficacy of etanercept, infliximab, and adalimumab. Manuscripts with fewer than 20 study subjects were excluded if other larger studies existed on the use of the same drug for a particular indication. Studies with <6 months of patient follow-up were also excluded, except in the case where no other data were available. Articles meeting these criteria were then reviewed by the three authors for inclusion in this review. RESULTS: Tumor necrosis factor inhibitors have been shown to decrease inflammation associated with a number of rheumatologic conditions. Three of the five commercially available TNF inhibitors-etanercept, infliximab, and adalimumab-have been studied for their efficacy in treatment of ocular inflammation. Etanercept appears to be inadequate in controlling ocular inflammation and is not recommended for the treatment of uveitis. Infliximab and adalimumab, however, have shown encouraging results in multiple trials. Serious potential side effects such as infection, including reactivation of latent tuberculosis, malignancy, and demyelinating disease, may limit the use of TNF inhibitors in uveitis. Proper screening of patients prior to initiating these therapies may decrease these risks. DISCUSSION: Early success with infliximab and adalimumab has paved the way for new TNF inhibitors and other corticosteroid-sparing drugs to emerge in the treatment of ocular inflammation. Future studies are on the horizon to determine the long-term safety and efficacy of newer TNF inhibitors such as certolizumab and golimumab.

Shortening ocular pain duration following intravitreal injections.

PURPOSE: To determine ocular pain duration after routine in-office intravitreal injection and to determine whether topical eyedrops are beneficial in increasing patient comfort. METHODS: Forty injection-naïve patients receiving routine intravitreal injections of bevacizumab for age-related macular degeneration were randomized into 3 groups: group 1 (control, no drops), group 2 (generic artificial tears), and group 3 (ketorolac tromethamine 0.4% eyedrops). Those who received topical medications were given a Visual Analog Pain score survey and asked to record their pain on a scale from 0 (no distress) to 10 (unbearable distress) daily until a score of 0 was achieved, at which point they were instructed to discontinue use of their given drops. Self-reported pain scores were assessed. RESULTS: Pain after routine intravitreal injection lasts on average between 3 and 7 days. Patients receiving topical ketorolac eyedrops reported the fewest average number of pain days (2.25±1.22) vs patients receiving artificial tears (3.54±1.13) or those who received no postprocedure eyedrops (5.13±1.25); p<0.05. At most, patients receiving ketorolac eyedrops reported 3 days of recordable pain. Those who received artificial tears reported at most 5 days of recordable pain, and patients who did not receive any postprocedure eyedrops reported at most 7 days of recordable pain. CONCLUSIONS: Pain after intravitreal injection is generally mild, may be reduced by postinjection topical ketorolac eyedrops, and lasts less than 1 week.

H1N1-associated acute retinitis.

PURPOSE: To present the first reported case of bilateral H(1)N(1)-associated acute retinitis and its successful treatment. DESIGN: Interventional case report. METHODS: A 41-year-old HIV-positive male presented with acute vision loss, panuveitis, and retinitis. A diagnostic and therapeutic vitrectomy with intravitreal injection of vancomycin and ganciclovir and endolaser was performed. One month later, the patient returned with similar symptoms in the fellow eye and underwent the same procedure. RESULTS: ELISA immunoassay revealed H(1)N(1) antibodies in both the vitreous and serum. PCR for herpes viruses included HSV, CMV, and VZV. Bacterial and fungal cultures were negative. On 1-year follow-up, the vision remained 20/20 in both eyes without evidence of recurrent inflammation. CONCLUSIONS: H(1)N(1) should be included in the differential diagnosis of any patient with a history of recent influenza A (H(1)N(1)) infection and acute retinitis. H(1)N(1) may carry a better prognosis than other viruses causing acute retinitis.

Factors affecting patients' pain intensity during in office intravitreal injection procedure.

PURPOSE: To determine factors associated with patients' comfort during routine in-office intravitreal injection. METHODS: Sixty patients receiving intravitreal injections over 15 months for macular edema because of diabetes, age-related macular degeneration, or retinal vein occlusion who were randomized into 3 groups to receive 1 of 3 commonly used forms of anesthesia-TetraVisc, proparacaine HCl, or tetracaine HCl-before receiving intravitreal injection were studied. Fifteen minutes after injection, patients were asked to rate their pain from 0 (no pain/no distress) to 10 (agonizing pain/unbearable distress) using a Visual Analog Pain score survey. Self-reported pain scores were stratified by age, gender, diagnosis, injection number, substance injected, needle gauge, and visual acuity improvement. RESULTS: Intravitreal injection was associated with low pain scores. Patients receiving tetracaine reported a statistically significant lower pain score (3.05 ± 2.01) than patients receiving proparacaine (3.17 ± 2.18) or TetraVisc (3.3 9± 2.26; P < 0.01). Other important factors influencing pain score significantly (P < 0.01) included improved vision from previous injection, female sex, and age >65 years. Pain scores decreased with each consecutive injection. CONCLUSION: Pain associated with intravitreal injection is generally mild, and may be associated with epidemiologic and environmental factors.

Teenage acute macular neuroretinopathy.

PURPOSE: To present the first case of acute macular neuroretinopathy in a teenager. METHODS: Case report, optical coherence tomography, fluorescein angiography, electroretinography. RESULTS: Optical coherence tomography, fluorescein angiography, and electroretinography were used to diagnose acute macular neuroretinopathy. Laboratory results were positive for HLA-B7. CONCLUSIONS: The rare diagnosis of acute macular neuroretinopathy should be considered in girls on oral contraceptives, with a recent history of acute viral illness, who present with acute rapid onset of multiple, paracentral scotomas.