Risk factors for development of anti-adalimumab antibodies in non-infectious uveitis.

Purpose: To evaluate risk factors associated with development of anti-adalimumab antibodies (AAA) in patients with non-infectious uveitis treated with adalimumab. Methods: A retrospective, cross-sectional, case-control study was done evaluating patients with non-infectious uveitis treated with adalimumab for at least 12 months and have undergone testing for AAA levels. Demographics, clinical characteristics, grading of ocular inflammation, and previous and concomitant immunomodulatory therapy were assessed. Univariate and multivariate analysis were done to estimate odds ratio (OR) with 95% confidence intervals for the various risk factors. Results: A total of 31 patients were included in the analysis, in which 12 patients who tested positive (Group 1) were matched with 19 patients who tested negative for AAA (Group 2). The groups differed significantly in terms of sex (female) (91.7% vs 52.6%, p = 0.046), presence of systemic disease (91.7% vs 42.1%, p = 0.008), and presence of anterior chamber inflammation at baseline (100% vs 63.2%, p = 0.026). A history of interruption in anti-TNF therapy prior to starting or restarting adalimumab was found to have an increased odds for development of AAA (OR 16.89 [2.92, 107.11], p = 0.008), as well as flare-ups (reactivation of disease) during adalimumab therapy (OR 6.77 [1.80, 61.80], p = 0.027). Weekly dosing of adalimumab was shown to decrease odds of AAA development (OR 0.34 [0.02, 0.70], p = 0.040), while concomitant anti-metabolite therapy was not shown to be a statistically significant protective factor (OR 2.22 [0.50, 9.96], p = 0.148). Conclusions: History of interruption in anti-TNF therapy and flare during adalimumab were associated with development of AAA, while weekly dosing of adalimumab was protective against AAA. Identification of those with higher risk of developing AAA may guide in clinical decision making to optimize management for these patients.

Importance of Baseline Fluorescein Angiography for Patients Presenting to Tertiary Uveitis Clinic.

PURPOSE: To ascertain whether the use of ultra-wide-field fluorescein angiography (UWFFA) at baseline visit alters the assessment of disease activity and localization, as well as the management of patients presenting to a tertiary uveitis clinic. DESIGN: Retrospective comparison of diagnostic approaches. METHODS: Baseline visits of 158 patients who presented to the Uveitis Clinic at the Byers Eye Institute at Stanford between 2017 and 2022 were evaluated by three uveitis-trained ophthalmologists (I.K., A.B., and H.G.). Each eye had undergone clinical examination along with ultra-wide-field fundus photography (UWFFP) (Optos Plc, Dunfermline, Scotland, UK), spectral-domain optical coherence tomography (SD-OCT, Spectralis Heidelberg, Heidelberg Engineering, Heidelberg, Germany) and UWFFA (Optos Plc, Dunfermline, Scotland, UK) at the baseline visit. Investigators were asked to successively determine disease activity, localization of disease (anterior, posterior or both), and management decisions based on clinical examination and UWFFP and SD-OCT (Set 1) and Set 1 plus UWFFA (Set 2). The primary outcome was the percentage of eyes whose management changed based on the availability of UWFFA, compared with Set 1. RESULTS: The mean age of the patients was 46.9±22.4 (range, 7-96) and 91 (57.6%) were female. With Set 1 alone, 138 (55.2%) eyes were found to have active disease; localization was anterior in 58 (42.0%) eyes, posterior in 53 (38.4%) eyes and anterior + posterior in 27 (19.6%) eyes. With Set 2, 169 eyes of 107 patients had active anterior, posterior or pan-uveitis. In comparison with Set 1, assessment with Set 2 identified additional 31 (18.3%) eyes with active disease (p=0.006), and additional 31 (18.3%) eyes having disease in both anterior + posterior segments (p<0.001). Regarding the primary outcome, management was changed in 68 (27.4%) eyes in Set 2, compared to Set 1. CONCLUSION: Baseline UWFFA may alter assessment of disease activity, localization, and management decisions compared to clinical examination with only UWFFP and SD-OCT for eyes with uveitis. Thus, UWFFA may be considered as an essential tool in the evaluation of uveitis patients at the baseline visit.

Intravenous cyclophosphamide therapy for patients with severe ocular inflammatory diseases who failed other immunomodulatory therapies.

BACKGROUND: Ocular inflammatory diseases, including scleritis and uveitis, have been widely treated with immunomodulatory therapies (IMTs) as a steroid-sparing approach. Such strategy includes conventional therapies (antimetabolites, alkylating agents, and calcineurin inhibitors) as well as biologic agents like adalimumab, infliximab, rituximab, and tocilizumab. Cyclophosphamide (CP) is an alkylating agent and mainly inhibits the functioning of both T and B cells. Though known to have potential adverse events, including bone marrow suppression, hemorrhagic cystitis, and sterility, CP has been shown to be efficacious, especially in recalcitrant cases and when used intravenous (IV) for a limited period. MAIN FINDINGS: We conducted a retrospective case-series to assess the safety and efficacy of CP therapy for patients with severe ocular inflammatory diseases who failed other IMTs. Medical records of 1295 patients who presented to the Uveitis Clinic at the Byers Eye Institute at Stanford between 2017 and 2022 were reviewed. Seven patients (10 eyes) who received CP therapy for ocular inflammatory diseases with at least one year of follow-up were included. The mean age of the patients (4 males, 3 females) was 61.6 ± 14.9 (43.0-89.0) years. Clinical diagnoses included necrotizing scleritis (5 eyes), peripheral ulcerative keratitis (2 eyes), orbital pseudotumor (1 eye), HLA-B27 associated panuveitis and retinal vasculitis (2 eyes). Ocular disease was idiopathic in 3 patients, and was associated with rheumatoid arthritis, IgG-4 sclerosing disease, dermatomyositis, and ankylosing spondylitis in 1 patient each. All the patients had history of previous IMT use including methotrexate (5), mycophenolate mofetil (3), azathioprine (1), tacrolimus (1), adalimumab (2), infliximab (4), and rituximab (1). The mean follow-up time was 34.4 ± 11.0 (13-45) months, and mean duration of CP therapy was 11.9 ± 8.8 (5-28) months. Remission was achieved in 5 patients (71.4%). Four patients (57.1%) experienced transient leukopenia (white blood cell count < 4000/mL). SHORT CONCLUSION: CP therapy can be considered a potentially effective and relatively safe therapeutic option for patients with severe ocular inflammatory diseases who failed other IMTs including biologics (TNFa and CD20 inhibitors).

Challenges for further successful development of tumor necrosis factor targeting therapies for uveitis.

INTRODUCTION: Uveitis is a heterogeneous group of ocular conditions characterized by inflammation of the uveal tract and is one of the leading causes of vision impairment. In developed countries, noninfectious uveitis (NIU) represents most cases and is challenging to treat due to its severity, chronicity, and high recurrence rates. The advent of anti-tumor necrosis factor-α (anti-TNF-α) agents have dramatically improved outcomes and changed treatment paradigms in NIU. AREAS COVERED: The index article summarizes the present experience of anti-TNF-α agents in NIU pharmacotherapy and highlights the barriers to further research and development of anti-TNF-α agents for uveitis. Common challenges faced in NIU clinical drugs trials, specific difficulties in anti-TNF-α drug development, and promising competitor drug candidates are discussed and evaluated. EXPERT OPINION: Anti-TNF-α agents have revolutionized NIU pharmacotherapy and greatly improved outcomes with good safety profiles. The great success of systemic infliximab and adalimumab in NIU treatment has resulted in little impetus for further development of this class of medication. Attempts have been made to deliver anti-TNF-α agents intravitreally but that has not been successful thus far. With expiring patents, competition from biosimilars and newer, novel molecules, it may not be viable to continue pursuing anti-TNF-α drug development.

Considerations in the management of ocular toxoplasmosis in pregnancy: a review of literature.

Ocular toxoplasmosis is the most common cause of infectious posterior uveitis. Available literature is still conflicting regarding the incidence of recurrence during pregnancy as various calculations were employed in the different published studies. Although earlier reports have suggested a difference in presentation and an increase in severity during pregnancy, newer studies appear to show otherwise. Further diagnostic testing, including serologic and intraocular fluid sampling, may be indicated to increase the diagnostic accuracy in this special population of patients. The management of ocular toxoplasmosis during pregnancy is challenging as the foetus is additionally considered in the choice of treatment. Traditionally preferred anti-toxoplasmosis regimens containing antifolate drugs, such as pyrimethamine and trimethoprim-sulfamethoxazole, cannot be used routinely in pregnant patients, especially during the first trimester. This review includes literature on alternative treatments for ocular toxoplasmosis during pregnancy, including spiramycin and intravitreal treatment options.

Recent advances in uveitis therapy: focus on selected phase 2 and 3 clinical trials.

INTRODUCTION: Uveitis is a heterogeneous group of ocular conditions characterized by inflammation of the uveal tract. It is a leading cause of blindness in developed countries and exerts significant psychological, social, and economic impact on both patients and the larger society. While there are numerous pharmacotherapy options, posterior segment noninfectious uveitis remains a significant challenge to treat due to its severity, chronicity, and high recurrence rates. AREAS COVERED: The index review highlights the unmet needs of uveitis pharmacotherapy and its research and the shortcomings of existing ocular and systemic therapeutic options for noninfectious uveitis. The more promising novel ocular drug delivery methods and therapeutic targets/drugs are discussed, and evidence from the clinical trials is evaluated. EXPERT OPINION: There has been incredible growth in the number of treatment options available to uveitis patients today, especially with the new generation of biologic drugs. Available evidence suggests that these newer options may be superior to conventional immunosuppressive therapies in terms of efficacy and side effect profiles. Further high-quality research and additional clinical trials will be needed to clarify their roles in the stepladder treatment approach of noninfectious uveitis.

Ocular tuberculosis masquerading as atypical ocular toxoplasmosis.

Ocular tuberculosis is a great mimicker of various uveitis entities. We present a case of a 29-year-old male who came in with blurring of vision and floaters in the left eye. On examination, the left eye had anterior chamber cells and vitritis associated with retinitis. He had no other symptoms. The initial presentation was consistent with ocular toxoplasmosis, and he was started on oral sulfamethoxazole-trimethoprim and showed a good response to the treatment. However, work-up revealed negative toxoplasma antibody titers but a positive M. tuberculosis interferon-gamma release assay test and Mantoux test, making the diagnosis of ocular tuberculosis more likely. The patient was shifted to antituberculous therapy, which eventually resulted in the resolution of the inflammation with a recovery of the visual acuity. The diagnosis of ocular tuberculosis requires a detailed medical history as well as microbiologic and immunologic studies. A high index of suspicion by the treating ophthalmologist is necessary to reveal the diagnosis.

Neurosarcoidosis, Coccidioidomycosis, or Both!

Purpose: To report a case of neurosarcoidosis (NS) who was initially diagnosed as Coccidioidomycosis immitis (CI) infection. Observations: A 57-year-old diabetic man presented with sudden painless diminution of vision, metamorphopsia, and color vision deficits in the left eye (OS) for one month. His vision was 20/20 in the right eye (OD) and 20/40 OS. Ophthalmic examination revealed left relative afferent pupillary defect, blurred optic nerve margin, creamy chorioretinal infiltration around the optic disc, and mild macular edema. OD examination was non-revealing. Chest CT scan with contrast showed calcified mediastinal lymph nodes, but biopsy of the lymph nodes was normal. Brain and orbit MRI demonstrated soft tissue abnormality with enhancement in left orbital apex with involvement of the extraocular muscles. CSF culture was negative, but complement fixation had positive titer of 1:2 for CI. The patient was diagnosed with CI meningitis, and antifungal therapy was initiated. Slight visual and symptomatic improvement was observed, which was not completely satisfactory. Biopsy of extraocular orbital muscle five months later revealed non-caseating granulomatous inflammation, leading to initiation of prednisone trial therapy. Nine months later, the patient was referred to a tertiary center owing to persistence of optic disc edema OS. PET CT was consistent with a diagnosis of sarcoidosis. Antifungal treatment was discontinued, and oral prednisone with methotrexate was initiated. Subsequently, methotrexate was replaced by infliximab to further manage ocular inflammation and neurologic symptoms which was effective. Vision was 20/20 OD and 20/30 OS at the most recent visit. Conclusion and Importance: Signs and symptoms of neurosarcoidosis and coccidioidomycosis can be similar and deceiving. The index case underscores importance of considering appropriate differential diagnoses in patients with similar symptoms and signs who may respond to preliminary designated treatment but not to the optimal extent. Considering such possibility could assist clinicians in managing the patients timely and efficiently.

Optical coherence tomography angiography analysis of changes in the foveal avascular zone in eyes with diabetic macular edema treated with intravitreal anti-vascular endothelial growth factor.

BACKGROUND: To analyze the changes in foveal avascular zone (FAZ) area, perimeter, and circularity in the superficial (SCP) and deep (DCP) capillary plexuses in eyes with diabetic macular edema (DME) treated with intravitreal anti-VEGF using optical coherence tomography angiography (OCTA). METHODS: This prospective observational study included 56 eyes from 32 patients with DME that received intravitreal anti-VEGF. OCTA images were obtained at baseline and 1, 3, and 6 months of follow-up. The outcome measures were FAZ area, perimeter, and circularity in both the SCP and DCP, as well as central subfield thickness (CST) and best-corrected visual acuity (BCVA). RESULTS: The mean number of intravitreal anti-VEGF injections received during the observation period was 4.60 ± 0.82 (range: 3-6). The FAZ area, perimeter, and circularity were statistically unchanged at all observation points in both the SCP (p = 0.772, p = 0.405, p = 0.157, respectively) and the DCP (p = 0.620, p = 0.769, p = 0.481, respectively). Despite having no change in the FAZ parameters, there was still a statistically significant decrease in CST (p < 0.001) as well as a statistically significant increase in BCVA (p = 0.004) during the observation period. CONCLUSIONS: The FAZ area, perimeter, and circularity in the SCP and DCP as measured by OCTA remained stable during the first 6 months of intravitreal anti-VEGF therapy in eyes with DME. While there were no significant changes in the FAZ, treatment with intravitreal anti-VEGF still resulted in decreased CST and improved BCVA.

Combined central retinal artery and vein occlusion following trabeculectomy.

Retinal vascular events may occur as rare complications of glaucoma procedures due to various factors, including exacerbation of ischemia in patients with pre-existing vascular comorbidities, toxic effect of mitomycin-C, and decompression retinopathy. We present the case of a 47-year-old hypertensive male who underwent trabeculectomy for advanced glaucoma in his right eye. At 3 weeks postoperatively, he presented with a drop in visual acuity to light perception with a spike in intraocular pressure. On examination, there was increased bleb vascularity as well as rubeosis. Fundoscopy revealed findings consistent with both central retinal artery occlusion and central retinal vein occlusion. Combined central retinal artery and vein occlusion is a rare retinal vascular condition. Neovascular glaucoma can occur as a sequelae of the ischemic process in the retina. Despite treatment, there is a poor visual prognosis, with the affected eye usually becoming blind from optic atrophy and neovascularization.

Changes in Retina Practice Patterns During the COVID-19 Pandemic in the Philippines.

PURPOSE: The aim of this study was to assess the changes in clinical practice patterns among retina specialists in the Philippines in response to the coronavirus disease 2019 (COVID-19) pandemic. MATERIALS AND METHODS: This was a multi-center cross-sectional study based on a self-reported online survey. An online questionnaire was distributed among practicing retina specialists in the Philippines as listed in the database of the Vitreo-Retina Society of the Philippines using a combination of convenience and snowball sampling. The questionnaire contained questions regarding changes in clinic set-up, laser procedures, intravitreal injections, vitreoretinal surgery, and long-term outlooks. RESULTS: A total of 48 responses were recorded and analyzed with a view rate of 41.7%. There was a decrease in the number of clinic consults, laser procedures, intravitreal injections, and vitreoretinal procedures with most reporting only 1-25% of their usual patient load. Several modifications in clinic protocols have been made, including use of personal protective equipment, adjustments in clinic hours, and scheduling of only urgent cases. The adjustments implemented during the pandemic are expected by most respondents to be long-term changes. CONCLUSION: Retina specialists in the Philippines have implemented changes in their practices to combat COVID-19, following guidelines issued by the local and international governing bodies on health.

Retinal vasoproliferative tumour secondary to retinitis pigmentosa sine pigmento.

Retinitis pigmentosa can be associated with exudative vasculopathy in rare instances, which can manifest as retinal vasoproliferative tumours. We present the case of a 33-year-old woman previously diagnosed with retinitis pigmentosa sine pigmentosa in both eyes. She was asymptomatic and just came in for a routine follow-up eye examination. Thorough examination of the peripheral retina on the right eye revealed a dome-shaped retinal tumour with a feeder vessel and surrounding exudative changes at the superotemporal periphery, consistent with a secondary retinal vasoproliferative tumour from retinitis pigmentosa. She subsequently underwent focal laser photocoagulation of the tumour which resulted in tumour stabilisation. While exudative vasculopathy is very uncommon in retinitis pigmentosa, ophthalmologists need to be aware of its occurrence in such patients. Vision loss may occur from exudation, haemorrhage, retinal detachment and neovascularisation. A thorough examination of the peripheral retina is warranted in these cases.

Tractional retinal detachment ('crunch' phenomenon) from intravitreal anti-vascular endothelial growth factor injection in central retinal vein occlusion.

Tractional retinal detachment is an uncommon complication of intravitreal anti-vascular endothelial growth factor (VEGF) injection wherein the drug triggers tractional retinal detachment as a result of fibrovascular membrane contraction. We present a case of a 42-year-old hypertensive woman diagnosed with chronic central retinal vein occlusion on both eyes. The right eye had total retinal detachment and neovascular glaucoma, while the left eye had retinal neovascularisation. Panretinal photocoagulation and intravitreal anti-VEGF injection was started on the left eye. However, she was lost to follow-up. She returned 4 months later with extensive tractional retinal detachment involving the macula on the left eye. She subsequently underwent vitrectomy with endolaser and silicone oil tamponade on the left eye. The anti-VEGF 'crunch' results from regression of fibrovascular proliferation with a concurrent increase in fibrosis, resulting in worsening retinal traction. With the widespread use of anti-VEGF agents, ophthalmologists need to be aware of this vision-threatening complication.

Corneal melt following corneal tattooing with carbon-based ink.

PURPOSE: to report a case of corneal melting following corneal tattooing with carbon-based ink. OBSERVATIONS: A 67 year old female with a phthisical eye underwent corneal tattooing with carbon-based ink for purpose of cosmesis. The procedure was uncomplicated. At 8 weeks postoperatively, she presented with almost complete corneal melt with uveal prolapse. There was no evidence of infection. The patient underwent evisceration. Histopathologic examination of the excised corneal button showed melting of the epithelium and anterior stromal layers, diffuse inflammation of the deeper stromal layers, and disorganized Descemet membrane and endothelium with adherent iris tissue. CONCLUSIONS AND IMPORTANCE: Corneal melting can occur as a rare complication of corneal tattooing with carbon-based ink.

Large graft tectonic penetrating keratoplasty in a case of severe aspergillus keratitis.

Penetrating keratoplasty is indicated for cases of severe microbial keratitis, particularly if associated with impending corneal perforation. The case report details a 45-year-old male farmer who consulted for blurring of vision in the left eye after an incident wherein mud was flung onto his eye during farming. He noted eye redness and a growing opacity on his left eye. He was initially treated with topical antimicrobial and corticosteroid medication which did not resolve his symptoms. He presented with a visual acuity of hand movement on the affected eye. Slit lamp examination showed a large protruding mound-like plaque, occupying almost the entire corneal surface of the left eye, with associated scleritis. The ocular ultrasound was unremarkable. The patient was diagnosed with fungal keratitis, which culture from corneal scraping showed to be from an infection with Aspergillus. A tectonic penetrating keratoplasty with 360-degree iridectomy, lens extraction, and anterior vitrectomy was immediately done, and a regimen consisting of topical natamycin was started. Despite the severe presentation of the fungal corneal infection, the eye was fortunately salvaged.

Transscleral cyclophotocoagulation as primary management in a nanophthalmic eye with anterior uveitis and secondary mixed mechanism glaucoma.

A 36-year-old woman presented with eye pain and blurring of vision in her right eye. On eye examination, it was noted that there were angle-closure glaucoma and anterior uveitis in both eyes. Ocular ultrasound showed short axial lengths as well as a choroidal thickening in both eyes, confirming the diagnosis of nanophthalmos. Nanophthalmos is a condition where the eye is abnormally short, resulting in axial hyperopia and predisposing it to angle-closure glaucoma. The patient was initially managed medically, but the glaucoma was intractable. The patient underwent repeated sessions of transscleral cyclophotocoagulation which eventually lowered the intraocular pressure. The management of nanophthalmic eyes can be quite challenging due to the risk of inciting uveal effusion syndrome with any form of intraocular surgery. Controlled and repeated sessions of transscleral cyclophotocoagulation may be considered as a viable management option in these cases.

Incidence and outcomes of ocular hypertension from rhegmatogenous retinal detachment surgery in the acute postoperative setting.

PURPOSE: To determine the incidence of ocular hypertension following surgery for rhegmatogenous retinal detachment in the first 3 months postoperatively and to determine their outcomes in terms of visual acuity, control of IOP, and changes in cup:disc ratio. PATIENTS AND METHODS: A single center prospective cohort study was done involving patients who underwent retinal surgery for rhegmatogenous retinal detachment. The patients were followed up for 3 months postoperatively and were monitored for development of ocular hypertension. The primary outcome measures were changes in IOP, visual acuity, and cup:disc ratio. RESULTS: Of the 52 eyes enrolled in the study, 19 eyes developed ocular hypertension in the first 3 months postoperatively, giving an incidence rate of 36.5% (95% CI, 48.9-76.0%). Analysis of mean IOP trends shows that most cases of IOP elevations occur in the first day postoperatively with a sustained elevation up to the first month and then returning to normal levels by the 3rd month. There is a significant increase in mean cup:disc ratio among patients who developed ocular hypertension (p=0.047). Visual acuity trends show that mean visual acuity significantly improved from baseline among cases who maintained normal IOP (p=0.002) as compared to those who developed ocular hypertension (p=0.97), although the difference in final visual acuity at the end of 3 months between groups was not statistically significant (p=0.30). CONCLUSION: Ocular hypertension may complicate retinal reattachment surgery. Control of IOP in the acute setting is essential to prevent development of secondary glaucoma.

Pyoderma gangrenosum of the upper eyelid.

A 3-year-old woman presented with a large ulcerated lesion involving the left upper eyelid and left earlobe with erythematous, swollen, undermined and advancing borders. Culture of the ulcer showed no growth of organisms. Treatment with empiric intravenous and topical antibiotics showed no improvement. Workup revealed an elevated white blood cell count with elevated neutrophil count, elevated erythrocyte sedimentation rate and C reactive protein and positive antinuclear antibody. A skin biopsy showed a neutrophilic dermatitis with vasculitis. The patient was started on oral prednisone, which resulted in halting of the progression of ulceration and clinically decreased skin inflammation. The skin biopsy and positive response to corticosteroids confirmed the diagnosis of pyoderma gangrenosum. Pyoderma gangrenosum is a rare inflammatory skin condition and rarely presents as lesions of the eyelid. Early initiation of immunosuppressive therapy prevents disfigurement. Eyelid reconstruction in these cases may prove to be difficult.