Vitreoretinal surgery in the management of infectious and non-infectious uveitis - a narrative review.

PURPOSE: This study aims to conduct a narrative review about the current role of vitreoretinal surgery in the management of infectious and non-infectious uveitis. METHODS: This review was performed based on a search of the PubMed database or on relevant published papers according to our current knowledge. RESULTS: A total of 91 articles were identified in the literature review. With the advance of microincision vitrectomy surgery (MIVS), pars plana vitrectomy (PPV) has gained increasing popularity in the management of infectious and non-infectious uveitis. For diagnostic purposes, larger amounts of sample can be obtained by MIVS than traditional vitreous aspiration using needles. For treatment purposes, PPV removes vitreous opacities, decreases inflammatory cytokines and mediators of inflammation, and tackles related complications, including hypotony, epiretinal membrane, macular holes, and retinal detachment. Achieving optimum control of inflammation prior to surgery is important for surgical interventions for non-emergent therapeutic indications and complications of uveitis. Peri-operative inflammation management is essential for decreasing the risk of surgical intervention. An overall complication rate of 42-54% was reported with cataract to be the leading cause of complications. CONCLUSION: Most reports affirm the role of PPV in the management of infectious and non-infectious uveitis, although the quality of data remains limited by a lack of applying standardized reporting outcomes, limitations in study design, and a paucity of prospective data.

Two Cases of Cutibacterium acnes (C acnes) Endophthalmitis Manifesting With Unusual Epiretinal Deposits.

This article describes two cases of delayed-onset Cutibacterium acnes (C acnes) endophthalmitis 1 month after cataract surgery manifesting with unusual epiretinal deposits. Both patients were referred for persistent inflammation after cataract surgery. After failing to respond to a vitreous tap with injection of antibiotics, the patients underwent pars plana vitrectomy and in one of the cases partial posterior capsulectomy for a posterior capsular plaque. Intraoperatively, both cases were found to have unusual multifocal epiretinal deposits. The clinical presentations described here represent a highly unique manifestation of C acnes endophthalmitis distinct from the classic anterior segment findings. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:164-167.].

Progress in the diagnosis of ocular sarcoidosis.

Sarcoidosis is a multisystem granulomatous inflammation that affects multiple organ systems. The spectrum of extraocular and ocular involvement is wide and may precede systemic involvement. The diagnosis of ocular sarcoidosis relies on a combination of clinical findings, laboratory investigations, and radiographic findings. These include but are not limited to serum angiotensin-converting enzyme (ACE), lysozyme, plain-film radiographs of the chest, computed tomography (CT) scans of the chest, pulmonary function testing, bronchoalveolar lavage, and retinal imaging among others. In this review, we highlight current and evolving systemic investigations and approaches to ophthalmic imaging when considering the diagnosis of ocular sarcoidosis.

Relationship of Epiretinal Membrane Formation and Macular Edema Development in a Large Cohort of Uveitic Eyes.

Purpose: To identify the temporal relationship and clinical characteristics of epiretinal membrane (ERM) and macular edema (ME) formation in uveitic eyes.Methods: A total of 269 subjects (444 uveitic eyes) met study inclusion criteria. Comprehensive ophthalmic examination, spectral domain-optical coherence tomography (SD-OCT), and clinical testing were carried out.Results: Of the 444 uveitic eyes, 229 eyes (51.6%) developed an ERM, whereas 87 eyes (19.1%) developed ME. The odds ratios (ORs) of systemic disease causing uveitis and resulting in ERM and ME were significantly higher in posterior uveitis (OR 6.56, 95% CI 2.98-14.46; p < .0001) and panuveitis (OR 10.09, 95% CI 4.05-25.15; p < .0001). Temporal analysis revealed that an ERM was noted concurrently or prior to ME development in 93.8% of eyes.Conclusions: ERM and ME are primarily observed in posterior uveitis and panuveitis associated with systemic diseases. The temporal relationship highlights the importance of characterization of ERM as it relates to the development of uveitic ME.

Revised criteria of International Workshop on Ocular Sarcoidosis (IWOS) for the diagnosis of ocular sarcoidosis.

AIMS: International criteria for the diagnosis of ocular sarcoidosis (OS) was established by the first International Workshop on Ocular Sarcoidosis (IWOS) and validations studies revealed certain limitations of the criteria. To overcome the limitations, revised IWOS criteria was established in an international meeting. This manuscript was aimed at reporting the revised IWOS criteria. METHODS: A consensus workshop was carried out to discuss and revise the IWOS criteria. The workshop was held on 27 April 2017, in Nusa Dua, Bali, Indonesia. Prior to the workshop, a questionnaire proposing revised criteria and consisting of one item for differential diagnosis, seven items for ocular clinical signs, 10 items for systemic investigations and three categories of diagnostic criteria was circulated to 30 uveitis specialists. Questionnaire items with over 75% support were taken as consensus agreement; items with below 50% support were taken as consensus disagreement and items with 50%-75% support were discussed at the workshop. Of the latter items, those supported by two-thirds majority in the workshop were taken as consensus agreement. RESULTS: The survey and subsequent workshop reached consensus agreements of the revised criteria for the diagnosis of OS as follows: (1) other causes of granulomatous uveitis must be ruled out; (2) seven intraocular clinical signs suggestive of OS; (3) eight results of systemic investigations in suspected OS and (4) three categories of diagnostic criteria depending on biopsy results and combination of intraocular signs and results of systemic investigations. CONCLUSIONS: Revised IWOS criteria were proposed by a consensus workshop.

Is it melanoma-associated retinopathy or drug toxicity? Bilateral cystoid macular edema posing a diagnostic and therapeutic dilemma.

PURPOSE: To report the clinical presentation, multimodal imaging, and management of a patient with metastatic melanoma who presented with cystoid macular edema (CME). OBSERVATIONS: We report a case of a 71-year-old Caucasian male with metastatic melanoma who presented with bilateral cystoid macular edema after being on treatment with a programmed T cell death ligand 1 inhibitor, MPDL3280, for 1 year. Multimodal imaging techniques, including color fundus photographs, autofluorescence, spectral domain optical coherence tomography (OCT), fluorescein angiography (Spectralis, Heidelberg, Germany), and spectral-domain OCT angiography (Zeiss; California, USA) were performed to evaluate the etiology of his CME and to monitor his response to treatment. Clinical examination and multimodal imaging revealed 1 + chronic vitreous cells, an epiretinal membrane, and mild macular edema in both eyes. Fundus autofluorescence showed paravenous hypoautofluorescence in the right eye and scattered hypoautofluorescent spots in the left eye. Optical coherence tomography angiography (OCTA) revealed mild drop out of superficial vessels in the peri-foveal region bilaterally. These findings were concerning for melanoma-associated retinopathy, drug-related uveitis, or activation of a previous chronic autoimmune process. The patient was started on prednisone 30 mg oral daily and ketorolac tromethamine 0.5% 1 drop four times daily. He was then treated with bilateral sustained-release dexamethasone intravitreal implants (Ozurdex). He had complete resolution of CME, and was tapered off of oral steroids within 6 weeks. CONCLUSIONS AND IMPORTANCE: Melanoma-associated retinopathy can be accompanied by CME, which presents a diagnostic and therapeutic dilemma in cases where a new drug has been recently initiated. By treating the condition locally, the ophthalmologist may be able to taper systemic immunosuppression more quickly.

INTRAVENOUS IMMUNOGLOBULIN IN THE TREATMENT OF JUVENILE RETINITIS PIGMENTOSA-ASSOCIATED CYSTOID MACULAR EDEMA AND UVEITIS.

PURPOSE: To evaluate the efficacy of intravenous immunoglobulin in the treatment of cystoid macular edema and uveitis caused by juvenile retinitis pigmentosa in a woman interested in planning a pregnancy. METHODS: Descriptive case report. A 25-year-old woman with retinitis pigmentosa presented with decreased visual acuity, interested in a second opinion. RESULTS: Intravenous immunoglobulin therapy was begun at 2-week intervals. Visual acuity improved from 20/100 to 20/70 by 6 weeks, where it stabilized for the remaining year. Serial optical coherence tomography imaging revealed marked improvement in cystoid macular edema after 2 treatments of intravenous immunoglobulin at 2 weeks of follow-up, with complete resolution noted at 4 months, a finding that persisted at 1 year of follow-up. CONCLUSION: Our findings support the use of intravenous immunoglobulin as a therapeutic option for the resolution of cystoid macular edema and management of uveitis secondary to juvenile retinitis pigmentosa.

Coexisting Phacoanaphylaxis and Choroidal Melanoma: An Unusual Intraocular Inflammation.

PURPOSE: To describe an unusual case of panuveitis in coexisting choroidal melanoma and phacoanaphylaxis. METHODS: Clinical records of the patient with intraocular melanoma and pathologic findings of the affected eye were reviewed. Composition of inflammatory infiltrates involving the tumor and lens was evaluated immunohistochemically. RESULTS: Histologically, tumor showed a choroidal mixed cell type malignant melanoma with infiltration of inflammatory cells. The globe also showed typical features of phacoanaphylaxis, characterized by disruptions of the lens capsule with zonal granulomatous inflammation. The inflammatory infiltration revealed the predominant presence of both cytotoxic T cells and histiocytes in phacoanaphylaxis and intra-tumoral inflammation. CONCLUSIONS: The current clinico-pathologic case report suggests that a long standing intraocular melanoma can present with phacoanaphylaxis. The immunophenotype of the inflammatory infiltrates at both sites, lens and the tumor, is similar, cytotoxic T cells and histiocytes, favoring a common immune inflammatory process directed at the tumor and the lens.

Acute hypotony maculopathy following the initiation of a topical aqueous suppressant in a patient with a history of panuveitis without prior filtering surgery.

PURPOSE: To report a case of profound hypotony maculopathy as a complication of single-agent glaucoma therapy in a patient with a history of panuveitis without previous filtering surgery. OBSERVATIONS: A 70-year old Hispanic male with a history of resolved bilateral panuveitis, chronic angle closure glaucoma, and pars plana vitrectomy was started on topical timolol 0.5% daily in the left eye for mildly elevated intraocular pressure (15 mmHg). The patient returned 1.5 weeks later with new onset hypotony (1 mmHg), chorioretinal folds, and cystoid macular edema in the same eye without associated signs of inflammation. The drop was discontinued. The patient returned 1 month later with normalized eye pressure and improved vision with near-resolution of chorioretinal changes on optical coherence tomography (OCT). CONCLUSIONS AND IMPORTANCE: Hypotony maculopathy is most commonly seen following glaucoma filtering surgery and ocular trauma. The development of hypotony maculopathy following the administration of topical glaucoma medication alone is rare. Our case is the first to our knowledge to describe the rapid onset of visually significant hypotony maculopathy characterized by profound OCT changes upon the administration of a single topical glaucoma agent in a patient without prior filtering surgery. Treatment with glaucoma medications in patients with complex ocular histories including uveitis and vitreoretinal surgery requires caution and close follow-up.

Multimodal Imaging in Sympathetic Ophthalmia.

PURPOSE: To show the current status of multimodal imaging and its role in supporting an early diagnosis of sympathetic ophthalmia. METHODS: The diagnosis is mainly clinical supported with ancillary investigations; mainly fluorescein angiography and others, including indocyanine angiography optical coherence tomography (OCT), OCT enhanced depth imaging, autofluorescence imaging, and ultrasonography. RESULTS: Various imaging modalities such as OCT, autofluorescence imaging and angiography are critical in the diagnosis and management of sympathetic ophthalmia. The clinician must make adequate use of such ancillary investigations in the management of the patients. CONCLUSIONS: Sympathetic ophthalmia is a rare, bilateral inflammation of the uveal tract following penetrating trauma or surgery in one eye. The intraocular inflammation requires a prompt diagnosis so that the treatment can be initiated as early as possible.

Vogt-Koyanagi-Harada disease.

Vogt-Koyanagi-Harada disease, a severe bilateral granulomatous intraocular inflammation associated with serous retinal detachments, disk edema, and vitritis, with eventual development of a sunset glow fundus, is an autoimmune inflammatory condition mediated by T cells that target melanocytes in individuals susceptible to the disease. Vogt-Koyanagi-Harada disease presents clinically in 4 different phases: prodromal, uveitic, convalescent, and recurrent, with extraocular manifestations including headache, meningismus, hearing loss, poliosis, and vitiligo, to varying degrees. There have been considerable advances in imaging modalities resulting in earlier diagnosis and improved understanding of this disease. Ocular coherence tomography has replaced other imaging modalities in the diagnosis of acute and chronic Vogt-Koyanagi-Harada disease by revealing exudative detachments of the retina in the acute stage, along with choroidal thickening and demonstrating choroidal thinning in the chronic stage. Treatment of this disease is initially with corticosteroids, with a transition to immunomodulatory drugs for long-term control. Patients with Vogt-Koyanagi-Harada disease can have good final outcomes if treated promptly and aggressively and thus avoid complications such as sunset glow fundus, cataracts, glaucoma, subretinal fibrosis, and choroidal neovascularization.

Comprehensive polymerase chain reaction assay for detection of pathogenic DNA in lymphoproliferative disorders of the ocular adnexa.

Infectious agents have been identified as a major cause of specific types of human cancers worldwide. Several microorganisms have been identified as potential aggravators of ocular adnexal neoplasms; however, given the rarity of these neoplasms, large epidemiological studies are difficult to coordinate. This study aimed to conduct an exhaustive search for pathogenic DNA in lymphoproliferative disorders (LPD) of the ocular adnexa in a total of 70 patients who were diagnosed with LPD of the ocular adnexa between 2008 and 2013. Specimens were screened for bacterial, viral, fungal, and parasitic DNA by multiplex polymerase chain reaction (PCR) and quantitative real-time PCR. Among cases of conjunctival mucosa-associated lymphoid tissue lymphoma, human herpes virus (HHV)-6, HHV-7, chlamydia, Epstein-Barr virus (EBV) and bacterial 16S ribosomal DNA were detected. In cases of IgG4-related ocular disease, similar pathogens were detected but in a larger number of patients. Our PCR assays detected DNAs of various infectious agents in tumor specimens, especially HHV6, HHV7, and EBV, with different positive rates in various types of LPD. Chronic inflammatory stimulation or activation of oncogenes from these infectious agents might be involved in the pathogenesis of LPD of the ocular adnexa.

Eye examination for early diagnosis of disseminated tuberculosis in patients with AIDS.

Choroidal tuberculosis is present in 5-20% of patients with disseminated tuberculosis, and point-of-care dilated binocular indirect ophthalmoscopy eye examination can provide immediate diagnosis. In geographical areas of high tuberculosis prevalence and in susceptible patients (CD4 counts less than 200 cells per µL) detection of choroidal granulomas should be accepted as evidence of disseminated tuberculosis. With training and proper support, eye screening can be done by HIV/AIDS clinicians, allowing early tuberculosis treatment. In regions with a high burden of tuberculosis, we recommend that eye screening be a standard part of the initial assessment of susceptible patients, including at a minimum all patients with HIV/AIDS with CD4 less than 100 cells per µL with or without eye symptoms, and with or without suspicion of disseminated tuberculosis.

Anterior Segment Ischemia in Viper Bite.

PURPOSE: To describe the clinical and histopathological features of post viper bite anterior segment ischemia. METHODS: Seven patients with ocular complications following viper bite referred to uveitis clinic had slit-lamp examination, intraocular pressure (IOP) measurement, and fundus evaluation. Iris and fundus fluorescein angiography was performed on 2 patients. Histopathological examination was performed on iris tissues collected during cataract surgery. RESULTS: Strikingly similar clinical findings were noted, including circumpupillary superficial iris atrophy, mid dilated fixed pupil, marked pigment dispersion, low IOP, and cataract. All clinical signs were noted only in the anterior segment; the posterior segment was normal. Histopathology of iris revealed atrophy of iris stroma, necrotic iris pigment epithelium, and infiltration of T lymphocytes and fibrous membrane. Poor visual outcome was noted in patients with low IOP. CONCLUSION: Viper bite victims presented with clinical and histopathological signs of anterior segment ischemia and secondary inflammatory signs mimicking uveitis.

Retinopathy in lupus transitioned to Kikuchi-Fujimoto disease.

PURPOSE: We present a patient with systemic lupus erythematosus with significant vaso-occlusive retinal findings mimicking antiphospholipid antibody syndrome, who developed Kikuchi-Fujimoto disease. OBSERVATIONS: Our patient was initially diagnosed with systemic lupus erythematosus with antiphospholipid antibody syndrome given consistent serologic markers and profound retinal vascular ischemia. However, on subsequent follow up, she presented with fever and lymphadenopathy and underwent lymph node biopsy, which declared histologic findings of Kikuchi-Fujimoto disease. Repeat markers for antiphospholipid antibody syndrome were negative and she was taken off lifelong anticoagulation. CONCLUSIONS AND IMPORTANCE: Systemic lupus erythematosus and Kikuchi-Fujimoto disease may have many similar features and even biomarkers, and given the potential overlap of presentation, clinicians must carefully distinguish between these diseases to prevent unnecessary treatment.

MULTIMODAL IMAGING OF THE RETINA AND CHOROID IN SYSTEMIC AMYLOIDOSIS.

PURPOSE: To present the multimodal imaging findings of four patients with systemic amyloidosis, renal failure, and chorioretinopathy. METHODS: Retrospective analysis of four patients presenting to four institutions with evidence of amyloid induced chorioretinopathy. Fundus photography, autofluorescence, and spectral domain optical coherence tomography findings were studied and are presented. RESULTS: Four patients with biopsy-proven systemic amyloidosis demonstrated progressive chorioretinal degeneration with color fundus photography and autofluorescent imaging. With spectral domain optical coherence tomography analysis, amyloidosis-induced chorioretinopathy was characterized by a widened choriocapillaris band, choroidal infiltration, diffuse photoreceptor dysfunction, and thinning of the outer nuclear layer. CONCLUSION: Multimodal imaging including spectral domain optical coherence tomography analysis in eyes of patients with systemic amyloidosis shows deposition in the choroid. The deposition may cause a secondary toxic and or barrier effect resulting in diffuse retinal pigment epithelium and photoreceptor dysfunction.

Outcome of Treatment of Uveitic Macular Edema: The Multicenter Uveitis Steroid Treatment Trial 2-Year Results.

PURPOSE: To evaluate the 2-year outcomes of uveitic macular edema. DESIGN: Longitudinal follow-up of a randomized cohort. PARTICIPANTS: At baseline, 148 eyes of 117 patients enrolled in the Multicenter Uveitis Steroid Treatment (MUST) Trial had macular edema, and 134 eyes of 108 patients completed 2-year follow-up. METHODS: Patients enrolled in the study were randomized to either systemic immunosuppression or intravitreal fluocinolone acetonide implant therapy. Macular edema was defined as thickening of the retina (center point thickness≥240 µm) on time-domain optical coherence tomography (OCT) of macula. MAIN OUTCOME MEASURES: Improvement in macular edema (≥20% reduction in central point thickness on OCT), resolution of macular edema (normalization of thickness on OCT), and best-corrected visual acuity (BCVA). RESULTS: Between randomization and 2-years' follow-up, 62% and 25% of eyes in the systemic and implant groups, respectively, received at least 1 supplemental regional corticosteroid injection. By 2-years' follow-up, macular edema improved in 71% of eyes and resolved in 60%. There were no differences between treatment groups in the proportion of eyes with macular edema improving (systemic therapy vs. implant, 65% vs. 77%; P=0.20) and resolving (52% vs. 68%; P=0.28), but eyes randomized to implant had more improvement in macular thickness (median decrease of 180 vs. 109 µm in the systemic therapy group; P=0.04). Eyes with baseline fluorescein angiographic leakage were more likely to improve than those without (76% vs. 58%; P=0.03). Overall, there was a mean 5-letter (1 line) improvement in BCVA at 2 years. Mean changes in BCVA from baseline at 2 years by macular edema response status were: resolution, +10 letters; improvement without resolution, +10 letters (P=0.92); little to no change, 6 letters (P=0.19); and worsening, -16 letters (worsening acuity; P=0.0003). CONCLUSIONS: About two thirds of eyes with uveitic macular edema were observed to experience improvement in the edema and visual acuity with implant or systemic treatment. Fluocinolone acetonide implant therapy was associated with a greater quantitative improvement in thickness. Fluorescein angiography leakage was associated with a greater likelihood of improvement in macular edema.

Pathogenesis and Pathology of Intraocular Tuberculosis.

Intraocular tuberculosis (TB) is an extremely paucibacillary form of extrapulmonary TB. It likely results from bacterial dissemination to the eye from lungs, localization in ocular tissues, followed later by reactivation and appearance of clinical signs. These have been partly demonstrated in the guinea pig model of ocular TB. Alternative hypotheses have been suggested but are not supported by adequate evidence. Mycobacterial recognition by macrophages and dendritic cells probably leads to activation of several immune pathways, primarily the Th1 and Th17 pathways, as in other TB infections. Histopathology of bacteriologically proven ocular TB tissues reveals granulomatous inflammation with central caseous necrosis containing occasional acid-fast organisms. Recent reports have also demonstrated intraretinal granuloma in the vicinity of retinal vessels and T-cell infiltration of epiretinal membranes, in cases of TB retinal vasculitis.