The role of complement in ocular pathology

Functionally active complement system and complement regulatory proteins are present in the normal human and rodent eye. Complement activation and its regulation by ocular complement regulatory proteins contribute to the pathology of various ocular diseases including keratitis, uveitis and age-related macular degeneration. Furthermore, a strong relationship between age-related macular degeneration and polymorphism in the genes of certain complement components/complement regulatory proteins is now well established. Recombinant forms of the naturally occurring complement regulatory proteins have been exploited in the animal models for treatment of these ocular diseases. It is hoped that in the future recombinant complement regulatory proteins will be used as novel therapeutic agents in the clinic for the treatment of keratitis, uveitis, and age-related macular degeneration

Evaluation of early and late presentation of patients with ocular mucous membrane pemphigoid to two major tertiary referral hospitals in the United Kingdom

PURPOSE: Ocular mucous membrane pemphigoid (OcMMP) is a sight-threatening autoimmune disease in which referral to specialists units for further management is a common practise. This study aims to describe referral patterns, disease phenotype and management strategies in patients who present with either early or established disease to two large tertiary care hospitals in the United Kingdom.\ud \ud PATIENTS AND METHODS: In all, 54 consecutive patients with a documented history of OcMMP were followed for 24 months. Two groups were defined: (i) early-onset disease (EOD:<3 years, n=26, 51 eyes) and (ii) established disease (EstD:>5 years, n=24, 48 eyes). Data were captured at first clinic visit, and at 12 and 24 months follow-up. Information regarding duration, activity and stage of disease, visual acuity (VA), therapeutic strategies and clinical outcome were analysed.\ud \ud RESULTS: Patients with EOD were younger and had more severe conjunctival inflammation (76% of inflamed eyes) than the EstD group, who had poorer VA (26.7%=VA<3/60, P<0.01) and more advanced disease. Although 40% of patients were on existing immunosuppression, 48% required initiation or switch to more potent immunotherapy. In all, 28% (14) were referred back to the originating hospitals for continued care. Although inflammation had resolved in 78% (60/77) at 12 months, persistence of inflammation and progression did not differ between the two phenotypes. Importantly, 42% demonstrated disease progression in the absence of clinically detectable inflammation.\ud \ud CONCLUSIONS: These data highlight that irrespective of OcMMP phenotype, initiation or escalation of potent immunosuppression is required at tertiary hospitals. Moreover, the conjunctival scarring progresses even when the eye remains clinically quiescent. Early referral to tertiary centres is recommended to optimise immunosuppression and limit long-term ocular damage.\ud \u

Incidence, presenting features, and diagnosis of cicatrising conjunctivitis in the United Kingdom

Cicatrising conjunctival disorders are uncommon, and are difficult to diagnose and manage. This study was designed to assess the annual incidence and underlying diagnosis of patients with cicatrising conjunctivitis (CC) within the United Kingdom

Blockage of complement regulators in the conjunctiva and within the eye leads to massive inflammation and iritis

The open environment of the eye is continuously subject to an influx of foreign agents that can activate complement. Decay-accelerating factor (DAF), membrane cofactor protein (MCP) and CD59 are regulators that protect self-cells from autologous complement activation on their surfaces. They are expressed in the eye at unusually high levels but their physiological importance in this site is unstudied. In the rat, a structural analogue termed 5I2 antigen (5I2 Ag) has actions overlapping DAF and MCP. In this investigation, we injected F(ab′)(2) fragments of 5I2 mAb into the conjunctiva and aqueous humor, in the latter case with and without concomitant blockage of CD59. Massive neutrophilic infiltration of the stroma and iris resulted upon blocking 5I2 Ag activity. Frank necrosis of the iris occurred upon concomitant intraocular blockage of CD59. C3b was identified immunohistochemically, and minimal effects were seen in complement-depleted animals and in those treated with non-relevant antibody. The finding that blockage of 5I2 Ag function in periocular tissues and within the eye causes intense conjunctival inflammation and iritis demonstrates the importance of intrinsic complement regulators in protecting ocular tissues from spontaneous or bystander attack by autologous complement