Hazlita Isa

New Developments in Corticosteroid Therapy for Uveitis

Corticosteroids remain the mainstay of the management of patients with uveitis. Topical corticosteroids are effective in the control of anterior uveitis, but vary in strength, ocular penetration and side effect profile. Systemic corticosteroids are widely used for the management of posterior segment inflammation which requires treatment, particularly when it is associated with systemic disease or when bilateral ocular disease is present. However, when ocular inflammation is unilateral, or is active in one eye only, local therapy has considerable advantages, and periocular injections of corticosteroid are a useful alternative to systemic medication and are very effective in controlling mild or moderate intraocular inflammation. More recently, the injection of intraocular corticosteroids such as triamcinolone have been found to be effective in reducing macular oedema and improving vision in uveitic eyes which have proved refractory to systemic or periocular corticosteroids. The effect is usually transient, lasting around 3 months, but can be repeated although the side effects of cataract and raised intraocular pressure are increased in frequency with intraocular versus periocular corticosteroid injections. This has led to the development of new intraocular corticosteroid devices which are designed to deliver sustained-release drugs and obviate the need for systemic immunosuppressive treatment. The first such implant was Retisert, which is surgically implanted (in the operating theatre) and is designed to release fluocinolone over a period of about 30 months. More recently, Ozurdex, a ‘bioerodible’ dexamethasone implant which can be inserted in an office setting, has completed phase III clinical trials in patients with intermediate and posterior uveitis. This implant lasts approximately 6 months, and has been found to be effective with a much better side effect profile than Retisert or intravitreal triamcinolone injection, at least for one injection.

Automated Identification of Exudates and Optic Disc Based on Inverse Surface Thresholding

This paper presents a new approach to detect exudates and optic disc from color fundus images based on inverse surface thresholding. The strategy involves the applications of fuzzy c-means clustering, edge detection, otsu thresholding and inverse surface thresholding. The main advantage of the proposed approach is that it does not depend on manually selected parameters that are normally chosen to suit the tested databases. When applied to two sets of databases the proposed method outperforms a method based on watershed segmentation.

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.

Clinical and Imaging Features of Lacrimal Gland Involvement in Granulomatosis with Polyangiitis.

PURPOSE Lacrimal gland involvement in granulomatosis with polyangiitis (GPA) commonly accompanies orbital disease, but occasionally may be the sole presentation preceding any other organ manifestation or systemic disease. Diagnosis of orbital GPA, especially in patients with lacrimal involvement as the initial presentation, can be difficult because of nonspecific clinical features and lack of diagnostic specificity on histologic and antineutrophilic cytoplasmic antibody (ANCA) testing. Orbital GPA can be associated with a high morbidity from potential visual loss or rapid progression of latent systemic disease, making early diagnosis important. The purpose of this study was to describe the clinical and imaging features of patients with lacrimal gland involvement secondary to GPA and to compare them with those of other orbital inflammatory conditions in the lacrimal gland fossa. DESIGN Retrospective, noninterventional comparative case series. PARTICIPANTS Two hundred forty-seven patients who had undergone orbital biopsy over a 21-year period were identified from the Institute of Ophthalmology Pathology database. Sixty-nine patients were found to have orbital inflammatory disease with lacrimal gland involvement, of whom 7 had a final diagnosis of GPA. METHODS Clinical and imaging features of patients with GPA were analyzed and compared with those of the non-GPA group. MAIN OUTCOME MEASURES Features associated with GPA. RESULTS The median age at presentation for GPA patients was 30 years (mean ± standard deviation, 36.7±16.7 years; range, 14-57 years). The interval from presentation to definitive diagnosis of GPA ranged from 3 to 20 months (mean, 12.1 months; median, 12 months). Sinonasal involvement was demonstrated in 43% and bony changes were demonstrated in 29% of patients with GPA. A higher proportion of patients with GPA demonstrated sinonasal involvement (P = 0.011) and bony destruction (P = 0.048) compared with non-GPA patients. CONCLUSIONS Associated sinonasal involvement and bony changes on imaging are highly suggestive of GPA and should prompt a full diagnostic workup. A high index of suspicion should be maintained, with repeated ANCA testing, biopsy, and imaging where indicated, especially in the younger age group.

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.

Prevalence and causes of phthisis bulbi in a uveitis clinic

identified. In the corresponding area, intense GFAP accumulation was observed (Fig. 1C). The macular region and the optic nerve head did not show any pathological thickening (Fig. 2A). In these areas, only slight GFAP expression was noted (Fig. 2B,C). GFAP is an intermediary filament expressed by Müller cells as a response to retinal injury (Lewis & Fisher 2003). Previously, it has been reported that postoperative GFAP accumulation is associated with impaired retinal function (Wallentén et al. 2008). In our study, intense GFAP accumulation was confined to the retinal area of 500 lm surrounding the retinal tack. The overall diameter consequently measured 1000 lm. However, in the areas predestined for electrical stimulation and transfer of electrical impulses including the macular region and the optic nerve, only slight GFAP accumulation was observed. The associated impairment of the retinal function plays a minor role since the GFAP up-regulation resolves over several months and the retinal function completely restores (Wallentén et al. 2008). Hence, the electrical stimulation would not be hampered after an adequate recovery period. In conclusion, the insertion of a retinal tack induces intense up-regulation of GFAP in the close vicinity of the retinal tack, whereas in regions predestined for electrical stimulation and its transfer, only slight GFAP accumulation was observed. References

A study on the ergonomic assessment in the workplace

Ergonomics has gained attention and take into consideration by the workers in the different fields of works recently. It has given a huge impact on the workers comfort which directly affects the work efficiency and productivity. The workers have claimed to suffer from the painful postures and injuries in their workplace. Musculoskeletal disorders (MSDs) is the most common problem frequently reported by the workers. This problem occurs due to the lack of knowledge and alertness from the workers to the ergonomic in their surroundings. This paper intends to review the approaches and instruments used by the previous works of the researchers in the evaluation of the ergonomics. The two main assessment methods often used for ergonomic evaluation are Rapid Upper Limb Assessment (RULA) and Rapid Entire Body Assessment (REBA). Popular devices are Inertial Measurement Units (IMU) and Microsoft Kinect.

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.