Norshamsiah Md Din

Evaluation of Retinal Nerve Fiber Layer Thickness in Eyes With Hypertensive Uveitis

IMPORTANCE Uveitic glaucoma is among the most common causes of irreversible visual loss in uveitis. However, glaucoma detection can be obscured by inflammatory changes. OBJECTIVE To determine whether retinal nerve fiber layer (RNFL) measurement can be used to detect glaucoma in uveitic eyes with elevated intraocular pressure (IOP). DESIGN, SETTING, AND PARTICIPANTS Comparative case series of RNFL measurement using optical coherence tomography performed from May 1, 2010, through October 31, 2012, at a tertiary referral center. We assigned 536 eyes with uveitis (309 patients) in the following groups: normal contralateral eyes with unilateral uveitis (n = 72), normotensive uveitis (Uv-N) (n = 143), raised IOP and normal optic disc and/or visual field (Uv-H) (n = 233), and raised IOP and glaucomatous disc and/or visual field (Uv-G) (n = 88). EXPOSURES Eyes with uveitis and elevated IOP (>21 mm Hg) on at least 2 occasions. MAIN OUTCOMES AND MEASURES Comparison of RNFL values between groups of eyes and correlation with clinical data; risk factors for raised IOP, glaucoma, and RNFL thinning. RESULTS Mean (SD) global RNFL was thicker in Uv-N (106.4 [21.4] µm) compared with control (96.0 [9.0] µm; P < .001) eyes and was thicker in Uv-N eyes with active (119.6 [23.2] µm) compared with quiescent (102.3 [20.8] µm; P = .001) uveitis, which in turn was not significantly different from control eyes (P = .07). Compared with Uv-N eyes, significant RNFL thinning was seen in all quadrants except the temporal in Uv-G eyes and significant thinning in the inferior quadrant of Uv-H eyes with no evidence of disc or visual field changes (P = .03). Risk factors for elevated IOP were male sex and anterior uveitis. Age, higher peak IOP, longer duration of follow-up, and uveitis-induced elevation of IOP were risk factors for glaucoma and RNFL defect. CONCLUSIONS AND RELEVANCE Screening for glaucomatous RNFL changes in uveitis must be performed during quiescent periods. Thinning of the inferior quadrant suggests that glaucomatous damage, more than uveitic ocular hypertension, is in fact occurring. Measurement of RNFL may detect signs of damage before disc or visual field changes and therefore identifies a subgroup that should receive more aggressive treatment.

Intraocular pressure elevation in uveitis

Raised intraocular pressure in uveitis, either due to the disease itself or secondary to treatment with steroids, is one of the most common causes of secondary glaucoma in clinical practice. There are currently no standardized criteria for the diagnosis nor guidelines for the management of raised intraocular pressure in uveitis. Intraocular pressure elevation may be due to any combination of several mechanisms and, as a result, the prognosis differs from primary glaucomas. In addition, the management of ongoing inflammation without elevating the intraocular pressure remains a challenge. Ideally, new anti-inflammatory agents should have better anti-inflammatory properties with safer intraocular pressure profiles, while sustained release medications to lower intraocular pressure would improve patient compliance.

Tissue interleukin-17 and interleukin-23 as biomarkers for orbital granulomatosis with polyangiitis

Orbital inflammatory diseases (OIDs) from various causes may have a similar clinical presentation, with orbital biopsy being a key investigation to assist with diagnosis. Granulomatosis with polyangiitis (GPA) is an idiopathic granulomatous inflammatory disease that forms part of the spectrum of antineutrophil cytoplasm antibody (ANCA)-associated vasculitis. When left untreated, GPA is an aggressive disease, can result in severe, permanent organ damage, and is potentially life threatening when vital organs are affected. The histologic diagnosis of granulomatosis with polyangiitis (GPA) in the orbit is often difficult because classic histologic featuresdnamely vasculitis and necrosisdoften with a negative ANCA serology, are not found in all patients at the time of clinical presentation, leading to a delay in diagnosis and detection of life-threatening systemic disease. This study was designed to determine whether inflammatory cellular markers such as T and B cell subsets, and cytokines such as interleukin (IL)-17 and IL-23 could be potential biomarkers in orbital biopsies to aid the diagnosis of GPA. This study adhered to the tenets of the Declaration of Helsinki and was approved by the Moorfields & Whittington Research Ethics Committee. Tissue biopsies of patients with suspected orbital inflammatory disease between 1988 and 2009 were included only if the diagnosis and management of their orbital disease was based on any 2 of the following: (1) clinical history, (2) clinical manifestations, (3) biochemical investigations, or (4) radiologic features. Patients for whom the diagnosis and management of their orbital disease was based entirely on the histologic appearance were excluded. All orbital biopsies were stained with hematoxylin and eosin (H&E) for cellular analysis. Orbital biopsies of orbital GPA, idiopathic inflammatory orbital disease (IIOD), and sarcoidosis were further analyzed for infiltrating cellular subsets using immunohistochemical staining for CD3, CD4, CD8, CD20, CD68, CD134, IL-17, IL-23, and B-cell activating factor receptors. Inflammatory cells and tissue changes were then counted, masked to the patients’ final clinical diagnosis, and compared between GPA and other OIDs. In the immunohistochemical analysis, comparisons were also made between ANCAnegative GPA orbital biopsies with IIOD and sarcoidosis (IþS), and between non-typical GPA biopsies (i.e., absent of necrosis or vasculitis) with IþS. We identified 239 orbital biopsies with 39 cases of orbital GPA. With H&E staining necrosis (odds ratio [OR], 2.40; P < 0.001) and vasculitis (OR, 1.33; P < 0.001) were found to be independently associated with the clinical diagnosis of GPA but were absent in up to one-third of cases. Cytokine staining for IL-17 (P < 0.001), IL-23 (P < 0.001), and CD68 (P < 0.001) was significantly greater in GPA biopsies compared with IþS (Table 1; Fig 1 available at www.aaojournal.org); IL-17 and IL-23 were also significantly elevated in ANCA-negative cases (IL-17 [P < 0.04] and IL-23 [P < 0.02]) and in biopsies with nontypical GPA features (IL-17 [P < 0.03], IL-23 [P < 0.02]) compared with IþS. In this study, therewere significant differences found between the histology of GPA compared with other OIDs. With H&E staining, vasculitis and necrosis were found to be associated independently with the diagnosis of orbital GPA, consistent with the histology of GPA in the lungs and kidneys. However, these features, which are typically associated with and required for the tissue diagnosis of GPA, were not observed in all orbital GPA biopsies in this study, suggesting that, although their occurrence is important in establishing the diagnosis, their absence may not exclude it and other markers are needed to establish a diagnosis of GPA. Inflammatory cytokines IL-17 and IL-23 as well as macrophages (CD68), were found to be significantly increased in GPA biopsies. Interleukin-17 is a proinflammatory cytokine produced by T helper (Th)17 cells, a subset of Th cells. Interleukin-17 has been demonstrated to be a potent mediator for neutrophil recruitment, cells responsible for the production of ANCA, and has been associated with several systemic inflammatory diseases, including systemic GPA. The significant increase in IL-23þ cells in GPA compared with both IIOD and sarcoidosis is particularly interesting. Interleukin-23 is produced by macrophages and dendritic cells and its role in inflammation is primarily established as a crucial factor in the development of Th17 and IL-17 cytokine production. Nevertheless, IL-23 alone has been shown to play a role in arthritis and osteoclast formation in animal studies, with resultant bone destruction, which is independent of IL-17. A similar mechanism might explain the sinoorbital bone destruction seen in GPA, which does not occur in orbital sarcoidosis or IIOD. In addition, IL-23 has been related to disease severity in ANCA-associated vasculitis, including GPA, where patients with increased levels of IL-23 had more active disease compared with those with low IL-23. Serum ANCA, which is associated closely with GPA, is used generally as a diagnostic tool for the disease. However, in our study, although cellular and cytokine activity were higher in GPA tissues, there was no difference found in the inflammatory cell count between ANCA-positive and ANCA-negative patients. This indicates that the inflammatory activity is similar in all GPA patients independent of their ANCA status. We also did not find any difference between tissues with typical GPA histology (i.e., presence of necrosis and vasculitis) and those with nontypical histology. This further underscores that nontypical histology in the orbit does not preclude the diagnosis of orbital GPA and that other markers are required to assist in the diagnosis. The significant presence of IL-17 and IL-23 in biopsies of ANCA negative cases and in biopsies with nontypical GPA features compared with OIDs highlights their value as biomarkers for the diagnosis of GPA and allows early detection of this disease. B-celleactivating factor receptors showed a significant presence in GPA compared with IIOD, although not with sarcoidosis. Bcelleactivating factor receptors are expressed on B-lymphocytes, and its activation is crucial to the survival and maintenance of mature B-cells. This prolonged B-cell survival and the increased ability of B-cells to remain active, might be a differentiating factor in the manifestations and severity of orbital GPA compared with IIOD. In conclusion, IL-17 and IL-23 seem to be useful biomarkers for the diagnosis of orbital GPA. Further studies in the role of these cytokines in the pathogenesis of GPA would be beneficial.

The influence of diabetes mellitus on the management and visual outcome of patients with uveitis

role of the ophthalmologist in the treatment of syphilitic uveitis as on the one hand ophthalmological symptoms are often isolated, and on the other hand, ophthalmology wards rank second in order of departments diagnosing the disease. Ophthalmologists, who are no longer familiar with disease, should be mindful to focus on specific lesions such as ASPPC, which is also the most frequent, so as not to misdiagnose the infection.

Raised Intraocular Pressure in Nonjuvenile Idiopathic Arthritis-Uveitis Children: Risk Factors and Effect on Retinal Nerve Fiber Layer.

Purpose:To determine risk factors for intraocular pressure (IOP) elevation and glaucoma in children with nonjuvenile idiopathic arthritis–related uveitis and any IOP-related changes in the retinal nerve fiber layer (RNFL) thickness. Patients and Methods:Clinical data were collected from children attending a tertiary referral uveitis clinic between May 2010 and October 2012. We assigned 206 eyes of 103 children into 32 normal eyes, 108 normotensive uveitics (NU), 41 hypertensive uveitics (HU: raised IOP without glaucomatous disc), and 25 glaucomatous uveitics (GU: raised IOP with glaucomatous disc). Risk factors for raised IOP, glaucoma and steroid response (SR) were evaluated and RNFL thickness across groups was compared with determine changes related to raised IOP. Results:IOP elevation occurred in 40 patients (38.8%) or 66/174 eyes with uveitis (37.9%); and SR occurred in 35.1% of all corticosteroid-treated eyes. Chronic uveitis was a significant risk factor for raised IOP [odds ratio (OR)=9.28, P=0.001], glaucoma, and SR (OR=8.4, P<0.001). Higher peak IOP was also a risk factor for glaucoma (OR=1.4, P=0.003). About 70% of SR eyes were high responders (IOP increase >15 mm Hg from baseline), associated with younger age and corticosteroid injections. Although no significant RNFL thinning was detected between HU and NU eyes, significant thinning was detected in the inferior quadrant of GU (121.3±28.9 &mgr;m) compared with NU eyes (142.1±32.0 &mgr;m, P=0.043). Conclusions:Children with chronic uveitis are at higher risk of raised IOP and glaucoma. Thinning of the inferior RNFL quadrant may suggest glaucomatous changes in uveitic children with raised IOP.

Central Retinal Artery Occlusion Following Central Retinal Vein Occlusion- A Case Report

A 73-year-old gentleman with diabetes mellitus was found to have impending central retinal vein occlusion (CRVO), on routine eye check-up. Despite initiation of anti-platelet agent, he developed ischaemic CRVO two months later, with severe macula oedema. His systemic investigations showed good diabetic control, no blood dyscrasia/hypercoagulable state, normal lipid profile and inflammatory markers. Echocardiogram was normal. A month later, arteriolar attenuation was noted with rubeosis irides, and fluorescein angiogram study confirmed central retinal artery occlusion (CRAO). After ruling out the systemic risk factors, we postulate two possible anatomical related patho-mechanism of CRAO following CRVO: 1, CRVO converts the retinal circulation into a closed loop, results in complete hemodynamic block of the retinal circulation, and hence secondary CRAO; 2, swollen retinal nerve fibres at the optic nerve head secondary to CRVO cause compression to the retinal artery at the level of the lamina cribrosa, this compression is further aggravated by the increased in intraocular pressure (IOP), and hence secondary CRAO.

Severe tuberculous retinal vasculitis in healthy adults

Abstract Ocular tuberculosis may be a presenting feature of tuberculous infection, especially with extensive occlusive retinal vasculitis among Asians. Being a curable disease, awareness of its presentation and high index of suspicion are paramount as prompt treatment can halt the disease progression and prevent visual loss. We presented three cases of ocular tuberculosis in young healthy adults who presented with progressive blurring of vision with florid retinal vasculitis seen on funduscopy. Two of them were with no bacillus Calmette-Guerin scar. Fundus fluorescein angiography confirmed the presence of occlusive vasculitis with extensive area of ischemia. All cases showed a raise in erythrocyte sedimentation rate and strongly positive Mantoux tests. Pan-retinal photocoagulation was given to all patients. Two cases responded well to anti-tubercular therapy followed by oral steroids and regained normal vision in both eyes. One patient was not started on anti-tubercular therapy as he requested to return to his native country for further treatment.