Decreased interleukin(IL)-35 Expression is Associated with Active Intraocular Inflammation in Vogt-Koyanagi-Harada (VKH) Disease

Purpose: Recent studies have reported that IL-35 has a protective effect in autoimmune disease. In this study, we explored the role of IL-35 in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease.

Methods: The IL-35/EBI3 and IL-35/P35 mRNA level was assayed by Real-Time PCR. The level of IL-35 in serum was detected by ELISA. PBMCs and monocyte-derived DCs were cultured with or without IL-35 and the concentration of IL-17, IL-10, IFN-γ, IL-6, TNF-α, and IL-1β in supernatants was tested by ELISA.

Results: The serum level of IL-35 is reduced in active VKH patients. The mRNA expression of the two subunits IL-35/EBI3 and IL-35/P35 in PBMCs from patients with active VKH was also decreased. IL-35 significantly inhibited IFN-γ and IL-17 expression and induced IL-10 production by PBMCs and inhibited IL-6 production by monocyte-derived DCs.

Conclusion: The current study suggests that a decreased IL-35 expression may be involved in the pathogenesis of VKH disease.     

The Role of IFN-alpha in Experimental and Clinical Uveitis

Purpose: IFN-α is the only treatment capable of inducing long-term remission in some patients with ocular Behçet’s disease. In this review, we focus on immune mechanisms of IFN-α in animal models and patients and compare the outcome of different clinical studies.

Methods: Review of literature using PubMed and Google and original data from rat models with monophasic/chronic or relapsing experimental autoimmune uveitis treated with IFN-α.

Results: The role of IFN-α and its effect on various cell types were investigated, in some cases with contradictory results. Some patients respond very well to IFN-α treatment, while others are non-responders, which was reflected in the uveitis rat models: relapsing uveitis was ameliorated, the monophasic/chronic disease even aggravated.

Conclusions: Despite intensive investigations in patients and animal models, the immune mechanisms explaining the therapeutic effect of IFN-α in ocular Behçet’s disease are not yet fully understood and need further investigation.     

Multiple Evanescent White Dot Syndrome Following Intradermal Influenza Vaccination

Purpose: To present a case report of MEWDS following an intradermal influenza vaccination.

Methods: Review of the clinical, laboratory, photographic, and angiographic records of a patient with MEWDS.

Results: 27-year-old female that presented to our clinic with photopsias OD. These symptoms began 2 weeks following an influenza intradermal vaccination.

Fundus examination and diagnostic testing were consistent with MEWDS.

Conclusion: While rare, MEWDS can occur following influenza vaccination.     

Retinal Pigment Epithelium Detachment in Acute Vogt–Koyanagi–Harada Disease: An Unusual Finding at Presentation

Purpose: To report the cases of two patients who presented with acute Vogt–Koyanagi–Harada (VKH) disease and associated retinal pigment epithelium detachment (PED).

Methods: 2 case reports. Case 1: A 22-year-old male patient complained of acute bilateral decrease in vision. Initial best corrected visual acuity (BCVA) was 20/63, OU. There was 1+ vitreous cells, OU, exudative retinal detachment (ERD) in the right eye (RE), and a macular deep yellow lesion suggestive of PED in the left eye (LE). Case 2: A 40-year-old female patient presented with bilateral vision blurring. BCVA was 20/40 in the RE and 20/32 in the LE. There was 1+ vitreous cells OU, bilateral optic disc swelling and retinal striae.

Results: Multimodal imaging showed features of acute VKH disease with associated PED in the two patients. ERD and PED resolved under oral prednisone and cyclosporine in both cases.

Conclusion: PED may rarely occur in acute VKH disease at presentation.     

Choroidal and Retinal Anatomical Responses Following Systemic Corticosteroid Therapy in Vogt–Koyanagi–Harada Disease Using Swept-Source Optical Coherence Tomography

Purpose: To assess structural changes in retina and choroid after systemic corticosteroid therapy in Vogt–Koyanagi–Harada (VKH) disease using swept-source optical coherence tomography (SS-OCT).

Methods: SS-OCT was conducted before treatment and during first-month follow-up in 16 eyes treated with systemic corticosteroids for active VKH. Retina was divided into five zones depending on pretreatment choroidal thickness (CT) of <100, >100 to <200, >200 to <300, >300 to <400 and >400μm, and changes in retinal thickness and CT after treatment in these zones were compared with baseline.

Results: Mean CT significantly improved from 83.1±8.75 to 156.4±62.73μm(p = 0.008) in the zone with pre-CT <100μm and significantly decreased from 336.1 ± 17.28 to 266.28 ± 81.39μm(p = 0.008) in the zone with pre-CT > 300μm.

Conclusions: We have shown choroidal remodeling in VKH. SS-OCT can serve as an important noninvasive tool in assessment of treatment response in patients with VKH disease.     

Total Corneal Melt in Patient with Porphyria Cutanea Tarda in Presence of Another Risk Factor

Purpose: To report a case of two siblings affected by porphyria cutanea tarda (PCT) presenting with varying severity of ocular disease and evaluation of difference in the presence of risk factors.

Methods: Case report

Result: A 42-year-old Indian male diagnosed with PCT and history of daily intake of alcohol, presented with sudden decrease in vision of right eye. Examination showed perforated cornea surrounded by rim of 360-degree avascular necrotic sclera, with no evidence of infection.

Similar systemic history was present in his elder brother. He did not consume alcohol and presented with mere localized scleral thinning. Since the patient’s sibling acted as a natural control for the evaluation of alcohol as an independent risk factor, the difference in severity of disease can be explained on the basis of difference in alcohol intake.

Conclusion: In the presence of progression of the disease, other risk factors like intake of alcohol should be evaluated.     

Vogt-Koyanagi-Harada Disease Associated with Hepatitis B Vaccination

Purpose: To report a case of Vogt–Koyanagi–Harada (VKH) disease associated with hepatitis B vaccination.

Methods: Case report.

Results: A 43-year-old Caucasian male presented with a three-week history of blurry vision, pain, photophobia, and redness in both eyes. Three days prior to the onset of symptoms, he had received the hepatitis B virus vaccine. Clinical evaluation revealed multifocal placoid lesions in the posterior pole, choroidal thickening, and serous macular detachment. Targeted laboratory investigations were negative for infectious or autoimmune markers. After treatment with oral corticosteroids, the patient had resolution of symptoms with near-total recovery of visual function. The patient later reported systemic findings of hearing loss, tinnitus, and integumentary changes. A diagnosis of VKH disease was made and inflammation was managed with oral corticosteroids followed by methotrexate for long-term disease control.

Conclusions: VKH disease is an inflammatory condition primarily affecting the choroid, retinal pigment epithelium, and outer retina. The underlying etiology is unclear, but it can be associated with a viral prodrome suggesting an infectious trigger in a genetically susceptible individual. Our case suggests that hepatitis B vaccination may trigger a similar inflammatory response.     

Clinical Profile,Ultra-Wide-Field Fluorescence Angiography Findings,and Long-Term Prognosis of Uveitis in Tubulointerstitial Nephritis and Uveitis Syndrome at One Tertiary Medical Institute in China

Purpose: To analyze the clinical features and long-term prognosis of uveitis in tubulointerstitial nephritis and uveitis (TINU) syndrome in a cohort of Chinese patients.

Methods: A total of 32 patients with TINU syndrome between 2000 - 2016 were analyzed retrospectively.

Results: Mild anterior inflammation was observed in all cases. Ultra-wide-field fluorescence angiography (UWFA) was conducted on 13 patients, and peripheral vascular leakage was observed in 22/26 eyes (84.62%) compared with active anterior chamber inflammation in 13/26 eyes (50%). Three patients received increased corticosteroid dosage therapy on their first episode of uveitis guided by UWFA had stopped steroids without recurrence.

Conclusion: The uveitis in TINU syndrome was mild. Corticosteroids were efficient in most cases, but a slower tapering and long-term treatment were required. UWFA is sensitive in detecting the activity of uveitis and might be useful in monitoring disease progression. Complete withdrawal of medication was difficult to achieve in some cases.     

Biologic Treatment Options for Retinal Neovascularization in Behçet’s Disease

Purpose: Relapsing ocular inflammation occurs in about 70% of patients with Behçet’s disease (BD) and can lead to permanent loss of vision. Neovascularization of the optic disc (NVD) or elsewhere in the retina (NVE) is a relatively uncommon but severe complication that lacks standardized treatment.

Methods: We report on the therapeutic use of anti-TNF monoclonal antibodies for BD-associated NVD and NVE in one pediatric patient (subcutaneous adalimumab) and one young man (intravenous infliximab). Also, we review the previously published experience on biologic therapeutic options, namely anti-TNF agents and interferon-alpha in a total of three and eight patients, respectively.

Results: A fast-onset therapeutic effect was observed in both patients leading to complete regression of neovascularizations.

Conclusions: Both options may lead to regression of neovascularization, thus preventing loss of vision, but comparative studies need to determine the optimal treatment for this sight-threatening complication of BD.     

Anterior and Intermediate Uveitis Following Yellow Fever Vaccination with Fractional Dose: Case Reports

Purpose: To describe two cases of anterior and intermediate uveitis following yellow fever vaccination with fractional dose.

Methods: Case report.

Results: Case 1: A 35 year-old healthy woman presented with unilateral anterior uveitis 10 days after the yellow fever vaccination. Testing excluded infectious and rheumatic diseases and the episode was fully recovered after a short course of topical treatment. Case 2: A 21 year-old previously healthy woman presented with blurred vision in the left eye (OS) 14 days after the yellow fever vaccination. The ophthalmic examination of the OS revealed intermediated uveitis. Testing excluded infectious and neurological diseases. After six weeks of treatment with oral prednisone, the ocular inflammation had resolved.

Conclusion: Physicians should be aware of the possibility of eye inflammation following the yellow fever vaccination.     

Evidence of retinal degeneration in Wolfram syndrome

Purpose: Wolfram syndrome is characterized by early onset diabetes mellitus, diabetes insipidus, deafness, and optic atrophy, but retinal degeneration has not been described as a major component of the phenotype. We present two cases with Wolfram syndrome and evidence of retinal degeneration.

Materials and Methods: Observational case series. Patients underwent complete ocular examinations as well as retinal imaging and electroretinography.

Results: Both patients had electroretinographic evidence of retinal dysfunction/degeneration in addition to optic atrophy with an otherwise normal-appearing retina.

Conclusions: Some patients with Wolfram syndrome have a mild retinal degeneration that may be a manifestation of the neuronal involvement that is present in this condition.     

A Study on Ocular Morbidity among Patients with Psoriasis Visiting a Tertiary Care Hospital in Karnataka,Southern India

Introduction: Psoriasis is a chronic immune-mediated disorder with predominantly dermatological manifestations and varying prevalence in different parts of the world. Data on the ocular features of this disease are limited. Hence, we aimed to estimate the burden of ocular disease in psoriatic patients in the Indian population.

Materials and methods: An interdisciplinary cross-sectional hospital-based observational study was conducted in South India, wherein an ophthalmological evaluation was performed for the patients with Psoriasis. The ocular features were recorded and compared with the severity of psoriasis using the Psoriasis Area Severity Index (PASI) score.

Results: Ocular morbidity was observed in 80% of the patients with psoriasis which increased with increasing duration (p = 0.004) and increasing PASI score (p < 0.001). Blepharitis and dry eye disease were common in our patients with psoriasis.

Conclusion: It is important to screen patients with psoriasis for ocular comorbidities so as to prevent sight-threatening complications.     

Rapid and Sustained Efficacy of Golimumab in the Treatment of Multirefractory Uveitis Associated with Behçet’s Disease

Purpose: To evaluate golimumab (GOL) efficacy in the management of Behçet’s disease (BD)-related uveitis.

Methods: We retrospectively collected data from 5 patients (8 eyes) with at least two recent relapses of uveitis, treated with GOL at the standard dose of 50 mg every 4 weeks.

Results: A complete control of intraocular inflammation was observed in 7/8 eyes (87.5%) at 12-month follow-up. The number of relapses 12 months before and after GOL initiation was 11 and 1, respectively. At baseline, four eyes had active retinal vasculitis (RV). At 3-month follow-up evaluation RV resolved in all eyes. Mean Best Corrected Visual Acuity was 6.93 ± 4.34 at baseline and 7.32 ± 3.87 at 12-months follow-up.

Conclusion: We confirm GOL efficacy in reducing intraocular inflammation in BD, both in term of reduction in the number of uveitis relapses and in achieving a prompt resolution of active RV.     

Challenging Treatment of Ocular Surface Squamous Neoplasia in Patients with Atopic Disease

Purpose: Few studies have described ocular surface squamous neoplasia (OSSN) and its association with atopic diseases and there is no consensus on the course of OSSN in atopic patients. We thereby report three patients with atopy and OSSN.

Methods: Retrospective case series.

Results: Three male patients with mean age of 73 presented with OSSN and history of atopy treated with immunosuppressant therapy. Their histories included atopic dermatitis and keratoconjunctivitis. All patients had treatment complicated by multiple surgeries, recurrences, or advanced disease. The patients initially received medical treatment with topical interferon-alpha-2b (IFNα2b). However, all the patients had recurrences and required modification of treatment including topical 5-fluorouracil (5-FU).

Conclusion: We report on three patients with a history of atopy whose OSSN presentation and course was challenging. Overall, our cases responded better to topical 5-fluorouracil compared to topical interferon-alpha-2b, but recurrences were common. These patients may benefit from more aggressive and long-term treatment.     

Polymerase Chain Reaction and Goldmann-Witmer Coefficient to Examine the Role of Epstein-Barr Virus in Uveitis

Purpose: To use polymerase chain reaction (PCR) and Goldmann-Witmer Coefficient (GWC) calculation to search for evidence that Epstein-Barr virus (EBV) causes uveitis.

Methods: A prospective cross-sectional study where participants with positive multiplex EBV PCR results were further investigated by: 1) real-time PCR for EBV viral loads (VL) and 2) EBV GWC.

Results: Eleven of 106 consecutive uveitis patients (10.4%) had positive multiplex PCR for EBV on aqueous humor sampling and 7/11 (63.6%) were HIV-positive. Only 4/10 (40%) cases had detectable intraocular EBV VLs which were always lower than the blood or plasma VL. EBV GWC was negative in all 10 cases tested. In 9/11 (81.8%) of these cases an alternative, more plausible cause of uveitis was identified.

Conclusion: We found no evidence of active intraocular replication or antibody production to prove that EBV caused uveitis in these cases. In most cases an alternative treatable cause of uveitis was identified.     

Neuroretinitis Secondary to Bartonella Henselae in a Patient with Myelinated Retinal Nerve Fibers: Diagnostic Dilemmas and Treatment

Purpose: To report an unusual case of Bartonella henselae neuroretinitis (BHNR) in a patient with myelinated retinal nerve fibers (MRNFs).

Methods: A 56-year-old male presented for a consultation, because of a decrease in visual acuity from his right eye. Onset was unclear and the patient was not sure if this was a new symptom.

Results: Fundoscopy revealed MRNF without any other clinical findings. After 2 weeks, the patient returned complaining of further visual acuity decrease. Fundoscopy disclosed macular star formation. The patient was treated with azithromycin. The visual acuity deteriorated to 20/400 and we added systemic corticosteroids with slight improvement of the visual fields but minimal visual gain to 20/160. Serology test results were positive for BH (IgG titers>1/256).

Conclusions: Co-existence of BHNR and MRNF can create diagnostic dilemmas. The presence of myelinated nerve sheath in combination with the expected swelling in neuroretinitis may have caused an irreversible mechanical nerve damage.     

Clinical Characteristics and Prognostic Factors in Ankylosing Spondylitis Associated Uveitis

Purpose: To identify the clinical features and prognostic factors of uveitis associated with ankylosing spondylitis (AS).

Methods: This retrospective, interventional case series study reviewed the medical records of 91 AS patients with uveitis.

Results: The characteristics of AS-associated uveitis included male preponderance (70%), average onset in the fourth decade, unilateral manifestation (87.9%), and vitreous involvement or retinal vascular leakage (36.3%). All patients had acute anterior uveitis. The best corrected visual acuity in logMAR improved from 0.8 ± 0.3 to 0.1 ± 0.2. The use of biologic agents was the only significant factor in the multivariate analysis. Patients with vitreous involvement/retinal vascular leakage were more likely to use systemic/peribulbar steroids for inflammation control, and achieved equally favorable visual outcome as in those without vitreous involvement/retinal vascular leakage.

Conclusion: The clinical characteristics and profile of visual prognostic factors suggest an association between the severity of ocular inflammation and systemic disease.     

Ultra-Widefield Fluorescein Angiography in Intermediate Uveitis

Purpose: To examine associations between pattern of vascular leakage on ultrawide-field fluorescein angiography (UWFFA) and visual acuity, cystoid macular edema (CME), and inflammatory activity in intermediate uveitis.

Methods: Single center cross-sectional, retrospective review of medical records, spectral domain optical coherence tomography (SD-OCT) and angiographic images of intermediate uveitis patients who underwent UWFFA over a 12-month period.

Results: Forty-one eyes from 24 patients were included. Twelve eyes (29%) exhibited peripheral leakage, 26 eyes (64%) had diffuse leakage and three eyes (7%) had no leakage. Diffuse leakage was associated with 0.2 logMAR worse visual acuity than peripheral leakage (p = 0.02). There was no statistically significant difference in the odds of having CME when diffuse leakage was compared to peripheral leakage.

Conclusion: UWFFA identifies retinal vascular pathology in intermediate uveitis not present on clinical examination. Diffuse retinal vascular leakage was associated with worse visual acuity when compared to peripheral and no leakage patterns.     

Enhanced Vitreous Imaging in Uveitis

Purpose: To study the structural visibility of the posterior vitreous cavity and vitreoretinal interface using Spectral Domain–Optical Coherence Tomography in patients with uveitis using conventional, Enhanced Depth Imaging (EDI), Combined Depth Imaging (CDI), and Enhanced Vitreous Imaging (EVI) techniques.

Methods: It was an observational cross-sectional study of 59 eyes of 33 patients between age group 12–72 years (Median 43) diagnosed as uveitis with posterior segment manifestations underwent OCT using conventional, EDI, CDI, and EVI techniques. The visibility of posterior vitreous was graded in all the techniques.

Results: A statistically significant difference was seen in posterior vitreous visibility on comparing all four techniques. EVI showed better visibility of posterior vitreous cavity compared to all other techniques (P < 0.001).

Conclusions: EVI technique provides better structural visibility of posterior vitreous compared to conventional, EDI, and CDI techniques.     

Amniotic Membrane Transplant for Bullous Keratopathy: Confocal Microscopy & Anterior Segment Optical Coherence Tomography

Purpose: To assess amniotic membrane retention after amniotic membrane transplant in bullous keratopathy patients and whether there were any corneal structural changes that may hinder further penetrating keratoplasty

Methods: A retrospective study including 22 patients who have undergone amniotic membrane transplant from 1 Jan 1998 till 30 Jun 2016. Confocal microscopy and anterior segment optical coherence tomography (ASOCT) were performed to assess the retention of amniotic membrane and to detect any corneal structural changes. The comparison was made with 5 controls who had bullous keratopathy awaiting endothelial keratoplasty.

Results: Patients had a mean follow-up of 61 ± 33.7 months. Pain reduction was significant (p < .001) although it did not significantly correlate with the regularity of the superficial, intermediate or basal epithelial layers, nor with the retention of the amniotic membrane. No long-term structural changes that may hinder future penetrating keratoplasty were detected.

Conclusion: This procedure is a safe and effective long-term treatment for symptomatic bullous keratopathy patients.