John H. Chang

Acute Anterior Uveitis and HLA-B27

Acute anterior uveitis is the most common form of uveitis. HLA-B27-associated acute anterior uveitis is a distinct clinical entity that has wide-ranging medical significance due to its ocular, systemic, immunologic, and genetic features. The association between HLA-B27 and the spectrum of HLA-B27-associated inflammatory diseases remains one of the strongest HLA-disease associations known to date. This review examines acute anterior uveitis with particular focus on HLA-B27-associated acute anterior uveitis, including the epidemiology, immunopathology, association with HLA-B27 and its subtypes, clinical features, complications, prognosis, and potential new therapies such as anti-TNFalpha therapy and oral HLA-B27-peptide tolerance. There have been substantial recent advances in both clinical and basic scientific research in this field, including studies of the various animal models of acute anterior uveitis and the HLA-B27 transgenic animals, and these are summarized in this review. To the ophthalmologist, HLA-B27-associated acute anterior uveitis is an important clinical entity that is common, afflicts relatively young patients in their most productive years, and is associated with significant ocular morbidity due to its typically recurrent attacks of inflammation and its potentially vision-threatening ocular complications. Furthermore, to the ophthalmologist and the internist, HLA-B27-associated acute anterior uveitis is also of systemic importance due to its significant association with extraocular inflammatory diseases.

Uveitis: a global perspective

Purpose: To study the patterns of uveitis in various geographic regions. Methods: A systematic literature review was performed using the MEDLINE database, from 1966 to present. Studies that satisfied our described selection criteria were analyzed to provide a global perspective on uveitis. Results: Twenty-two studies, which were the best available representatives of Australia, North and South America, Europe, Asia, and Africa, were included in the final analysis. The distribution of uveitis cases according to the anatomical site of inflammation in the various regions, and the causes and clinical disease associations of anterior, intermediate, posterior, and pan-uveitis were studied for each of the regions and a comparative analysis was performed. Conclusions: There are similarities and distinct differences in the patterns of uveitis in the various geographic regions. Such patterns of uveitis are influenced by combinations of geographical, environmental, and genetic factors.

Epidemiology of uveitis.

Uveitis refers to inflammation of the uvea, the middle vascular coat of the eye, and is the most common cause of inflammatory eye disease and an important cause of blindness and visual impairment in most communities. The annual incidence of uveitis is between 17 and 52 per 100,000 population, and the prevalence is 38 to 714 cases per 100,000 population. It has been estimated that uveitis accounts for about 10% of the visual handicap in the Western world, and up to 35% of all uveitis patients have been reported to suffer significant visual impairment or legal blindness. As uveitis often afflicts the young adult population in their most productive years of life, the personal and population burden of this sight threatening disease is significant. Knowledge of the different types and etiology of uveitis in various populations is important in the diagnosis and treatment of inflammatory eye disease. There has been a significant increase in our understanding of the pathogenesis and epidemiology of uveitis in the past decade, and this review will attempt to summarize current understanding of these important features of this common disease.

Toll-like receptors in ocular immunity and the immunopathogenesis of inflammatory eye disease

Microbial agents have an important role in the pathogenesis of various inflammatory eye diseases, such as uveitis and keratitis. Microbial infections of the eye such as microbial keratitis, ocular onchocerciasis, bacterial endophthalmitis, viral retinitis, and other infectious uveitis are unfortunately common. In addition, microbial agents have been implicated in the pathogenesis of “non-infectious” immune mediated diseases such as HLA-B27 associated acute anterior uveitis. Toll-like receptors (TLR) are a family of pattern recognition receptors that initiates rapid host innate immune response to microbial components known as pathogen associated molecular patterns, which are unique to a given class of microbes, such as lipopolysaccharide of Gram negative bacteria. Recent in vitro and in vivo studies have demonstrated the expression and function of TLRs in the eye, with significant implications for better understanding of ocular immunity and the pathogenesis of inflammatory eye diseases affecting the cornea, uvea, and retina.

Use of ocular hypotensive prostaglandin analogues in patients with uveitis: does their use increase anterior uveitis and cystoid macular oedema?

Aim: A retrospective comparative case series was studied to determine whether the use of prostaglandin (PG) analogues to treat raised intraocular pressure (IOP) in patients with uveitis resulted in an increase in the frequency of anterior uveitis or cystoid macular oedema (CMO). Methods: 163 eyes of 84 consecutive patients with uveitis and raised IOP treated with a PG analogue at two tertiary referral uveitis clinics were identified over a 3-month period. Control eyes were selected as those uveitic eyes of the same patients, which were treated with topical IOP-lowering agent(s) other than a PG analogue. Pretreatment IOP was compared with the mean IOP during PG analogue treatment. The frequency of anterior uveitis and CMO during PG analogue treatment was compared with the frequency of these complications in the control eyes during non-PG IOP-lowering treatment. Results: Significant IOP reductions were observed during PG analogue treatment. There was no significant difference in the frequency of anterior uveitis in those eyes treated with PG analogues and those treated with non-PG agents (p = 0.87, Fisher exact test). None of the 69 uveitic eyes without a previous history of CMO developed this complication. There was no increase in the frequency of visually significant CMO during PG treatment compared with that during non-PG treatment (p = 0.19, Fisher exact test). Conclusion: This study demonstrates that PG analogues are potent topical medications for lowering raised IOP in patients with uveitis and are not associated with increased risk of CMO or anterior uveitis.

Short-term Safety and Efficacy of Intravitreal Triamcinolone Acetonide for Uveitic Macular Edema in Children

OBJECTIVES To evaluate the short-term safety and efficacy of intravitreal (IV) triamcinolone acetonide (TA) for treating pediatric cystoid macular edema (CME) secondary to noninfectious uveitis. METHODS A retrospective noncomparative interventional case series. The medical records of 15 consecutive children (16 eyes) with uveitic CME treated with IVTA (2 or 4 mg) were reviewed. Data collected included details of uveitis, CME, visual acuity, intraocular pressure, and cataract development. The median follow-up time was 16 months (range, 9-36 months). RESULTS Resolution of CME was achieved in all of the treated eyes. The median time taken for CME to resolve was 3 weeks (range, 1-24 weeks). The mean improvement of visual acuity after IVTA was 0.6 logarithm of the minimum angle of resolution. Following initial response to IVTA, CME relapsed in 5 eyes (31%) after a median time of 7 months (range, 3-13 months). The most common adverse effect was increased intraocular pressure, with an increase of more than 15 mm Hg in 5 eyes (31%). Steroid-induced cataract was observed in 6 of 11 phakic eyes (55%). CONCLUSIONS We found that IVTA is efficacious in the treatment of uveitic CME in children and results in CME resolution and visual acuity improvement. As in adults, treatment in children may be associated with elevated intraocular pressure and cataract.

What Is New HLA-B27 Acute Anterior Uveitis?

Acute anterior uveitis (AAU) is the most common form of uveitis, accounting for approximately 90% of all cases. Half of all cases of AAU are HLA-B27 positive. The disease is typically acute in onset, unilateral, nongranulomatous inflammation involving the iris and ciliary body, with a tendency to recurrent attacks. Approximately 50% of all patients with HLA-B27 AAU develop an associated seronegative arthritis (SNA), while approximately 25% of the patients initially diagnosed with HLA-B27 SNA develop AAU. Environmental factors play a critical role in the pathogenesis of AAU; in particular, bacterial triggers have been strongly implicated in the development of this disease. Topical corticosteroids and cycloplegic agents remain the cornerstones of treatment for AAU. Salazopirine and methotrexate are effective in decreasing recurrent attacks. Biological agents such as anti-TNF and anti-CD20 therapy may be effective in refractory severe AU but are rarely required.

Toric Implantable Collamer Lens for high myopic astigmatic Asian eyes.

PURPOSE To evaluate early visual outcomes, refractive outcomes, and complications of the Toric Implantable Collamer Lens (TICL) for the correction of high myopic astigmatism in Asian eyes. DESIGN Prospective, nonrandomized clinical study. PARTICIPANTS Forty-four eyes of 29 patients with myopia (spherical equivalent) between 6 and 18.25 diopters (D), and 1 and 4.5 D of astigmatism. METHODS Implantation of TICL. MAIN OUTCOME MEASURES Uncorrected visual acuity (UCVA), manifest refraction, best spectacle-corrected visual acuity (BSCVA), and postoperative complications. RESULTS At 6 months postoperatively, 70.59% of eyes had 20/20 or better UCVA and 68.57% had postoperative UCVA better than or equal to preoperative BSCVA. At baseline, no eyes had refractive cylinder <1 D; however, postoperatively 77.14% of eyes had <1.00 D of refractive cylinder. The mean refractive cylinder changed from 2.64 D (+/-0.91) preoperatively to 0.59 D (+/-0.51) postoperatively. Sixty percent of eyes were within 0.50 D and 85.71% of eyes were within 1.00 D of the targeted cylinder correction. Baseline manifest refraction spherical equivalent (MRSE) changed from -13.18 D (+/-2.41) to 0.00 D (+/-0.42) postoperatively. The number of eyes within 0.50 D and 1.00 D of the predicted MRSE were 82.86% and 97.14%, respectively. A BSCVA of 20/15 occurred in 45.71% of eyes postoperatively compared with 22.86% of eyes preoperatively. A BSCVA of 20/20 or better occurred in 94.29% postoperatively compared with 77.14% preoperatively. Postoperatively, 1 eye (2.86%) lost 1 line of BSCVA and none lost >1 line of BSCVA. Thirty-one percent of eyes gained 1 line of BSCVA and 8.57% gained 2 lines of BSCVA postoperatively. Misalignment of TICL axis occurred in 2 eyes of 2 patients. CONCLUSIONS The visual outcomes, refractive outcomes, and predictability are comparable with the United States Food and Drug Administration data on TICLs in non-Asian eyes. Safety concerns were not identified.

The role of PAMPs and DAMPs in the pathogenesis of acute and recurrent anterior uveitis

The pathogenesis of acute and recurrent anterior uveitis is poorly understood. Here, recent evidence is presented for the hypothesis that this disease may be associated with activation of receptors of the innate immune system, such as Toll-like receptors, by pathogen associated molecule patterns, such as lipopolysaccharide, derived from triggering gram negative bacteria. Acute anterior uveitis results in ocular tissue damage and the release of endogenous molecules (damage associated molecular patterns), such as heat shock proteins and S100 proteins that can also activate Toll-like receptors and thus perpetuate or reactivate intraocular inflammation.

Pythium insidiosum keratitis in an Australian child

A 3‐year‐old girl from the Northern Territory developed suppurative keratitis after swimming in pools. A mycelial organism suspected to be Pythium insidiosum was cultured. Treatment with polyhexamethylene biguanide and voriconazole for 5 days was unsuccessful, and a corneal graft was performed. The infection was cleared and when last seen 14 months after surgery the patient had a stable graft and useful vision. The identification of the organism was confirmed by rRNA gene sequencing. P. insidiosum is an oomycete, an organism more closely related to kelp than to fungi. Masses of hyphae were seen in sections and, for the first time, the ultrastructure of P. insidiosum in human tissue is described. The staining characteristics of cultured hyphae were assessed; lactofuchsin and acridine orange were found to be the most useful methods. Although the diagnosis of P. insidiosum keratitis is not difficult, and the organism is susceptible in vitro to a number of antimicrobial agents, early corneal transplantation remains the treatment of choice.