David M. Hinkle

Current treatments for radiation retinopathy

Abstract Background. To review the currently available therapeutic modalities for radiation retinopathy (RR), including newer investigational interventions directed towards specific aspects of the pathophysiology of this refractory complication. Methods. A review of the literature encompassing the pathogenesis of RR and the current therapeutic modalities available was performed. Results. RR is a chronic and progressive condition that results from exposure to any source of radiation. It might be secondary to radiation treatment of intraocular tumors such as choroidal melanomas, retinoblastomas, and choroidal metastasis, or from unavoidable exposure to excessive radiation from the treatment of extraocular tumors like cephalic, nasopharyngeal, orbital, and paranasal malignancies. After the results of the Collaborative Ocular Melanoma Study, most of the choroidal melanomas are being treated with plaque brachytherapy increasing by that the incidence of this radiation complication. RR has been reported to occur in as many as 60% of eyes treated with plaque radiation, with higher rates associated with larger tumors. Initially, the condition manifests as a radiation vasculopathy clinically seen as microaneurysms and telangiectases, with posterior development of retinal hard exudates and hemorrhages, macular edema, neovascularization and tractional retinal detachment. Regrettably, the management of these eyes remains limited. Photodynamic therapy, laser photocoagulation, oral pentoxyphylline and hyperbaric oxygen have been attempted as treatment modalities with inconclusive results. Intravitreal injections of anti-vascular endothelial growth factor such as bevacizumab, ranibizumab and pegaptanib sodium have been recently used, also with variable results. Discussion. RR is a common vision threatening complication following radiation therapy. The available therapeutic options are limited and show unsatisfactory results. Further large investigative studies are required for developing better therapeutic as well as preventive treatment strategies.

Bilateral uveitis associated with fluoroquinolone therapy.

Context: Retrospective case series, database study and literature review. Forty case reports are described. Objective: To report a possible association between fluoroquinolones and uveitis. Materials and Methods: Spontaneous reports from the National Registry of Drug-Induced Ocular Side effects, World Health Organization, and Food and Drug Administration were collected on uveitis associated with systemic fluoroquinolone therapy. A literature review was performed using keywords “uveitis”, “fluoroquinolones”, and each individual fluoroquinolone name. Additional case reports were collected from the practices of six uveitis subspecialists and one neuro-ophthalmologist. Main Outcome Measures: Data garnered from the reports include the type of fluoroquinolone, age, gender, adverse drug reaction (ADR), dosage, duration of therapy until onset of uveitis, concomitant drugs, systemic disease, dechallenge and rechallenge data. Results: A total of 40 case reports of uveitis associated with fluoroquinolones were identified including 12 men, 27 women, and 1 case in which the gender was not specified. The median age was 54 years. Dosage varied between the different fluoroquinolone drugs, with the median dosage within the range recommended in the package insert for each different fluoroquinolone. Median time from beginning of therapy to appearance of the ADR was 13 days (range 0–20 days). Thirteen patients were 60 years or older, and one patient was taking systemic anti-inflammatory steroids. There were five positive dechallenge case reports. Discussion: According to World Health Organization criteria, the relationship between fluoroquinolone therapy and uveitis is “possible”. Causality assessments are based on the time relationship of drug administration, uveitis development, and dechallenge data. Conclusions: Clinicians should be aware of a possible bilateral fluoroquinolone-associated uveitis, particularly the finding of iris transillumination and pigment dispersion.

The spectrum of fundus autofluorescence findings in birdshot chorioretinopathy.

Objective. To describe the diverse patterns observed with the use of autofluorescence fundus photography (FAF) in patients with Birdshot chorioretinopathy (BSCR). Methods. A chart review of patients with BSCR seen at the Massachusetts Eye Research and Surgery Institution, who had autofluorescence fundus photography. The data obtained included age, gender, presence of the HLA-A29 haplotype, and current treatment. Results. Eighteen eyes with HLA-A29 associated BSCR were included. Four eyes presented with active inflammation. Correspondence of the lesions noted in the colour fundus photograph was observed in 3 eyes which were more easily identified with the FAF. Fifteen eyes had fundus lesions more numerous and evident in the FAF than in the colour fundus photograph. Conclusion. Because FAF testing provides valuable insight into the metabolic state of the PR/RPE-complex, it may serve as a useful noninvasive assessment tool in patients with posterior uveitis in which the outer retina-RPE-choriocapillaries-complex is involved.

Pars plana vitrectomy in the management of paediatric uveitis: the Massachusetts Eye Research and Surgery Institution experience

PurposeTo assess the effectiveness and safety of pars plana vitrectomy (PPV) in the management of chronic paediatric uveitis.MethodsWe reviewed records of patients 16 years old or younger who underwent PPV due to persistent uveitis. Data including inflammatory status, ocular findings, visual acuity, dosage and duration of various medical therapies, surgical techniques and complications were collected.ResultsTwenty-eight eyes of 20 patients were included in the study. The diagnoses of uveitis included pars planitis in 15 eyes (54%), idiopathic panuveitis in 8 eyes (29%), and juvenile idiopathic arthritis-associated iridocyclitis in five eyes (18%). Six eyes presented with associated retinal vasculitis. The mean age at the time of PPV was 11.2 years. The mean follow-up after surgery was 13.5 months. All 28 eyes had active uveitis with or without medical therapy at the time of PPV. At last follow-up, uveitis control was achieved with or without adjuvant medical therapy in 27 eyes (96%). These included five of the six eyes with persistent retinal vasculitis. Two eyes that had 20-G PPV developed intra-operative retinal tears. Four eyes with pre-operative clear lenses developed cataract within the first 6 months after PPV.ConclusionsPPV is effective and safe in the management of chronic paediatric uveitis and its complications. It was able to reduce the amount of systemic medications required to control inflammation in this study. Patients with uveitis complicated by retinal vasculitis, however, are more likely to require long-term medical therapy to achieve inflammatory control.

Uveitis and Systemic Inflammatory Markers in Convalescent Phase of Ebola Virus Disease

We report a case of probable Zaire Ebola virus–related ophthalmologic complications in a physician from the United States who contracted Ebola virus disease in Liberia. Uveitis, immune activation, and nonspecific increase in antibody titers developed during convalescence. This case highlights immune phenomena that could complicate management of Ebola virus disease–related uveitis during convalescence.

Cytomegalovirus Retinitis in Immunocompetent Patients: Case Reports and Literature Review

Purpose: The purpose of this study was to examine 2 cases of cytomegalovirus (CMV) retinitis, occuring in 2 immunocompentent adult patients. Methods: Case selection and literature review. Results: Both patients cited significantly decreased vision despite systemic, topical, and/or local corticosteroid use. Neither patient was using high-dose immunosuppressant therapy at the time of diagnostic testing. Both patients exhibited confirmed CMV infection via polymerase chain reaction DNA testing. Oral antivirals were employed and have stabilized both patients. Conclusion: The cases described herein serve to inform ophthalmologists of the urgent need to include CMV in their differential when encountering an immunocompetent adult with significant comorbidities or with a history of previous exposure. Proper treatment is heavily reliant on proper diagnosis.

Local Treatment for Lymphoid Malignancies of the Eye

Lymphoid malignancies may affect the eye either as primary intraocular lymphomas (PIOL), or by secondary involvement of a nodal lymphoma. PIOL is a subtype of primary central nervous system (CNS) lymphoma and in up to 98% of the cases are non-Hodgkins B cell lymphomas. PIOL may occur in isolation, without involvement of the CNS. They may affect both the vitreous and the retina, while secondary invasion predominantly affects the uvea. Both forms frequently masquerade as intraocular inflammation or uveitis. Systemic chemotherapy, alone or in combination with radiotherapy has been used in the past for the treatment of PIOL. Methotrexate and rituximab are immunomodulatory agents used in the treatment of cancer and autoimmune diseases. Recent reports have shown the intraocular safety and efficacy of both of these agents for the treatment of PIOL.

Tubulointerstitial nephritis and uveitis syndrome.

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare immune-mediated disorder involving both the kidney and the eye. The disease usually is seen in children and female young adults and is caused by a variety of agents, including drugs, infections, and systemic or immune-related diseases. Renal involvement in TINU syndrome is primarily one of tubulointerstitial edema and infiltration by inflammatory cells. Ocular involvement in this disorder is typically a bilateral, anterior, nongranulomatous uveitis. However, posterior segment involvement with granulomatous inflammation has also been reported. Uveitis may precede, follow, or occur concomitantly with nephritis.

Biologic agents in experimental autoimmune uveitis

Experimental uveitis models were developed in an effort to elucidate the pathogenesis of human uveitis. The therapeutic effects of numerous anti-inflammatory agents including corticosteroids and immunomodulatory agents including biologic response modifiers have been investigated in both experimental and human uveitis. Monoclonal antibodies to tumor necrosis factor alpha and anti-interleukins, among others, demonstrate efficacy and are employed in the treatment of uveitis refractory to conventional immunomodulatory agents.

Moxifloxacin Concentration and Proteomic Analysis of Aqueous Humor in Human Uveitis Associated with Oral Moxifloxacin Therapy

Purpose: The aim was to report the aqueous humor moxifloxacin concentration and proteome profile of an individual with bilateral uveitis-like syndrome with pigment dispersion. Methods: Multiple reactions monitoring mass spectrometry quantified the aqueous concentration of moxifloxacin in the affected individual. Shotgun proteomic analysis performed via liquid chromatography tandem mass spectrometry (LC-MS/MS) defined the protein profile in the affected individual and unaffected control samples. Results: Moxifloxacin was present at higher than expected levels in aqueous humor 18 days following oral administration. One-third of the proteins were identified by significantly lower spectral counts in the aqueous of the individual with moxifloxacin associated uveitis compared to the unaffected control. Conclusion: Moxifloxacin was detected in aqueous humor 18 days following the completion of oral administration. These results suggest that moxifloxacin toxicity may be responsible for the uveitis-like syndrome with pigment dispersion syndrome induced by moxifloxacin therapy.