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.

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.

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.].

One-Year Follow-Up in a Phase 1/2a Clinical Trial of an Allogeneic RPE Cell Bioengineered Implant for Advanced Dry Age-Related Macular Degeneration.

Purpose: To report 1-year follow-up of a phase 1/2a clinical trial testing a composite subretinal implant having polarized human embryonic stem cell (hESC)-derived retinal pigment epithelium (RPE) cells on an ultrathin parylene substrate in subjects with advanced non-neovascular age-related macular degeneration (NNAMD). Methods: The phase 1/2a clinical trial included 16 subjects in two cohorts. The main endpoint was safety assessed at 365 days using ophthalmic and systemic exams. Pseudophakic subjects with geographic atrophy (GA) and severe vision loss were eligible. Low-dose tacrolimus immunosuppression was utilized for 68 days in the peri-implantation period. The implant was delivered to the worst seeing eye with a custom subretinal insertion device in an outpatient setting. A data safety monitoring committee reviewed all results. Results: The treated eyes of all subjects were legally blind with a baseline best-corrected visual acuity (BCVA) of ≤ 20/200. There were no unexpected serious adverse events. Four subjects in cohort 1 had serious ocular adverse events, including retinal hemorrhage, edema, focal retinal detachment, or RPE detachment, which was mitigated in cohort 2 using improved hemostasis during surgery. Although this study was not powered to assess efficacy, treated eyes from four subjects showed an increased BCVA of >5 letters (6-13 letters). A larger proportion of treated eyes experienced a >5-letter gain when compared with the untreated eye (27% vs. 7%; P = not significant) and a larger proportion of nonimplanted eyes demonstrated a >5-letter loss (47% vs. 33%; P = not significant). Conclusions: Outpatient delivery of the implant can be performed routinely. At 1 year, the implant is safe and well tolerated in subjects with advanced dry AMD. Translational Relevance: This work describes the first clinical trial, to our knowledge, of a novel implant for advanced dry AMD.

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.

Animal Models of Ocular Tuberculosis: Implications for Diagnosis and Treatment.

The pathogenesis of ocular tuberculosis (TB) has remained unclear due to the challenges of performing mechanistic studies on clinical samples. Animal models have the potential to bridge these gaps by providing information about ocular dissemination and localization of mycobacteria, innate and adaptive immune response, and granuloma formation in the eye. Here, we critically review various animal models of ocular TB from the early 20th century to date and derive novel insights into pathogenesis of ocular TB that have direct implications on the diagnosis and treatment of this disease. Future directions on experimental approaches to understanding pathogenesis of ocular TB are also discussed.

Incidence, prevalence, and risk factors of infectious uveitis and scleritis in the United States: A claims-based analysis.

BACKGROUND: Ocular inflammation causes significant visual morbidity in the United States, yet little is known about the epidemiology of infectious uveitis and scleritis. This study aims to evaluate the epidemiology of infectious uveitis/scleritis employing a large national medical claims database. METHODS: This was a retrospective, case-control study, employing Optum's de-identified Clinformatics® Data Mart Database, containing data from 21.5 million privately insured individuals with enrollment for at least 15 months within 2007-2015. Inclusion in the uveitis/scleritis sample required an index uveitis/scleritis diagnosis based on International Classification of Diseases, Ninth Revision (ICD-9) codes. Exclusion criteria included index date within 3 months after intraocular surgery. Rates for uveitis/scleritis were determined by anatomic site. Multivariable logistic regression analyses were performed to determine odds ratios for the incidence and prevalence of uveitis/scleritis by anatomic category. FINDINGS: Infectious etiologies accounted for less than 20% of uveitis/scleritis, with mean rates of 18.9 (incidence) and 60.6 (prevalence) per 100,000 persons. The mean prevalences of infectious anterior, intermediate, posterior, panuveitis, and scleritis were 27.7, 0.17, 23.4, 4.4, and 4.6, per 100,000, respectively. Overall risk of prevalent infectious uveitis/scleritis increased with age (OR>3.3 for each decade over age 18, p<0.01), female sex (OR = 1.2, p<0.01), non-Hispanic white race (OR<1 for all other races, p<0.01), as well as the East South Central census division (OR = 1.2, p<0.01), comprising Alabama, Kentucky, Missouri, and Tennessee. Medical comorbidities, including HIV infection (OR = 6.4, p<0.01) and rheumatologic disease (OR = 1.9, p<0.01), were common in the infectious uveitis/scleritis cohort. CONCLUSIONS: The incidence and prevalence of infectious uveitis/scleritis in the United States were higher than previously reported estimates but remained lower than in developing countries. Rates varied by age, sex, race, and medical comorbidities, and may reflect differential susceptibility to various infectious agents with disparate geographic distributions within the United States.

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.

Comparison of surgical outcomes of trabeculectomy, Ahmed shunt, and Baerveldt shunt in uveitic glaucoma.

BACKGROUND: Uveitis is defined as a collection of syndromes involving intraocular inflammation which can lead to pain, tissue damage, and vision loss. Ophthalmic surgery in uveitis patients can be challenging due to inflammation-induced fibrosis and scarring. Trabeculectomy and implantation of glaucoma drainage devices (aqueous shunts) have been used in surgical management of uveitic glaucoma, however there is a paucity of literature examining the comparative results of these entities in this unique setting. The purpose of this retrospective comparative study is to compare clinical outcomes of trabeculectomy with MMC, Ahmed shunt, and Baerveldt shunt surgery specifically in uveitic glaucoma. RESULTS: Median IOP, IOP reduction, glaucoma medication use, and visual acuity at 6- and 12-month follow-up were similar across groups. Postoperative hypotony rate was significantly different across trabeculectomy (53%), Baerveldt (24%), and Ahmed (18%) groups (p = 0.027); other complication rates were similar. Baerveldt eyes had a lower failure rate compared to trabeculectomy (p = 0.0054) and Ahmed (p = 0.0008) eyes. CONCLUSIONS: While there was no difference in IOP reduction between trabeculectomy, Ahmed, and Baerveldt, Baerveldt eyes had the lowest failure rate.

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.

Distinguishing Features of Ocular Sarcoidosis in an International Cohort of Uveitis Patients.

PURPOSE: To determine which clinical features distinguish ocular sarcoidosis from other forms of uveitis in an international population and to estimate the sensitivity and specificity of the International Workshop on Ocular Sarcoidosis (IWOS) clinical signs and laboratory tests. DESIGN: Multicenter, retrospective medical record review. PARTICIPANTS: Eight hundred eighty-four patients with uveitis from 19 centers in 12 countries. METHODS: Data collected included suspected cause of uveitis, clinical findings, and laboratory investigations within 6 months of presentation. The IWOS criteria were used to classify patients as having definite (biopsy-proven), presumed (evidence of bilateral hilar lymphadenopathy [BHL] on chest radiograph or CT scan), probable, or possible ocular sarcoidosis. Patients with biopsy positive results or BHL on chest radiograph or CT scan were considered sarcoidosis cases. MAIN OUTCOME MEASURES: Sensitivity and specificity of clinical signs and laboratory investigations for diagnosing ocular sarcoidosis. RESULTS: Of the 884 uveitis patients, 264 (30%) were suspected to have ocular sarcoidosis. One hundred eighty patients (20%) met the IWOS criteria; 98 were definite (biopsy-proven) disease, 69 presumed disease (BHL), 10 probable disease, and 3 possible disease. Among sarcoidosis cases, the most common clinical signs were bilaterality (86%); snowballs or string of pearls (50%); mutton-fat keratic precipitates, iris nodules, or both (46%); and multiple chorioretinal peripheral lesions (45%). Sixty-two percent of sarcoidosis cases had elevated angiotensin converting enzyme or lysozyme and 5% demonstrated abnormal liver enzyme test results. Of the patients suspected of having sarcoidosis, 97 (37%) did not meet the IWOS criteria. CONCLUSIONS: With the exception of BHL, IWOS clinical findings and investigational tests had low sensitivities for diagnosing ocular sarcoidosis. In particular, liver function tests seem to have little usefulness in diagnosing ocular sarcoidosis. Many patients suspected of having sarcoidosis did not fit into the classification system, indicating that the guidelines may need to be reconsidered. Adding novel laboratory tests and using more advanced statistical methods may lead to the development of a more generalizable classification system.

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.

Rabbit model of ocular indirect photodynamic therapy using a retinoblastoma xenograft.

PURPOSE: The goal of this project was to demonstrate the feasibility of coupling the indirect ophthalmoscope laser delivery system with the 690 nm wavelength diode laser used to perform photodynamic therapy (PDT) in the treatment of retinoblastoma. METHODS: For phase 1, a total of six pigmented rabbits were treated with the indirect laser delivery system. The laser source was provided by the Lumenis Opal 690 nm laser unit, delivered through a 810 nm Indirect ophthalmoscope headpiece and a hand-held 28-diopter indirect lens (1.0 mm spot size). Four rabbits received intravenous verteporfin at doses of 0.43 or 0.86 mg/kg, and two rabbits did not receive verteporfin (controls). A second phase of the study involved eight rabbits using a retinoblastoma xenograft to determine the effect of indirect PDT on subretinal tumors. RESULTS: For phase 1, a total of 20 laser treatments were performed in the right eyes of six rabbits. Laser power levels ranged between 40 and 150 mW/cm2 and treatment duration ranged between 1 and 3 min. In the four rabbits that received verteporfin, focal retinal scars were noted at 40 mW/cm2 and higher power levels. In the two control rabbits that did not receive verteporfin, thermal burns were confirmed at 75 mW/cm2 and higher power levels. Histopathology showed focal retino-choroidal scars at the site of PDT treatment, without evidence of generalized ocular damage. Using the retinoblastoma xenograft, the indirect PDT system was shown to cause areas of tumor necrosis on histopathology. CONCLUSIONS: The results of this pre-clinical study suggest verteporfin may be activated in the rabbit retina with the indirect delivery system and the 690 nm laser unit (i.e., Indirect PDT). Using verteporfin, treatment effects were observed at 40-50 mW/cm2 in the rabbit retina, while photocoagulation was achieved at 75 mW/cm2 and higher power levels. Fundoscopic and histopathologic examination of treated areas showed circumscribed areas of retinal damage and a lack of generalized ocular toxicity, suggesting that this modality may represent a safe and localized method for treating intraocular retinoblastoma.

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.

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.

Quadruple Neoplasms following Radiation Therapy for Congenital Bilateral Retinoblastoma.

PURPOSE: The aim of this study was to describe a 34-year-old male with hereditary bilateral retinoblastoma treated with radiotherapy as a child who developed 4 distinct tumors within the radiation field. METHODS: A 34-year-old male with bilateral retinoblastoma status postradiation therapy and recurrence requiring enucleation presented with left-eye visual acuity changes. Magnetic resonance imaging demonstrated a left orbital mass and a right parasellar complex lobulated mass (right sphenoid and right cavernous sinus). Two weeks later, the patient underwent excision of the orbital mass and biopsy of an upper-lid nodule. This was followed by craniotomy for removal of the complex mass. RESULTS: Histology revealed 4 distinct tumors, including an undifferentiated pleomorphic sarcoma (left orbit), a radiation-induced meningioma (right sphenoid), a schwannoma (right cavernous sinus), and a basal-cell carcinoma (left lid). CONCLUSION: Although occurrence of a second neoplasm is a well-known outcome following radiation treatment in patients with hereditary retinoblastoma, the diagnosis of 4 additional neoplasms is rare. Pleomorphic sarcoma, radiation-induced meningioma, and schwannoma are uncommon tumors and not well represented in the literature describing irradiated retinoblastoma patients. Secondary malignancies are a leading cause of early death in retinoblastoma survivors, and long-term follow-up is crucial for patient care.