Assessment and management of dry eye disease.

The topic of the 1984 Cambridge Ophthalmological Symposium was 'The Dry Eye'; it was chaired by my colleague and mentor Mr Peter Wright. In the 33 years that have passed since then we have learned a great deal more about this condition. This short paper sets out to review some of the more recent developments.

BSACI guideline for the diagnosis and management of allergic and non-allergic rhinitis (Revised Edition 2017; First edition 2007).

This is an updated guideline for the diagnosis and management of allergic and non-allergic rhinitis, first published in 2007. It was produced by the Standards of Care Committee of the British Society of Allergy and Clinical Immunology, using accredited methods. Allergic rhinitis is common and affects 10-15% of children and 26% of adults in the UK, it affects quality of life, school and work attendance, and is a risk factor for development of asthma. Allergic rhinitis is diagnosed by history and examination, supported by specific allergy tests. Topical nasal corticosteroids are the treatment of choice for moderate to severe disease. Combination therapy with intranasal corticosteroid plus intranasal antihistamine is more effective than either alone and provides second line treatment for those with rhinitis poorly controlled on monotherapy. Immunotherapy is highly effective when the specific allergen is the responsible driver for the symptoms. Treatment of rhinitis is associated with benefits for asthma. Non-allergic rhinitis also is a risk factor for the development of asthma and may be eosinophilic and steroid-responsive or neurogenic and non- inflammatory. Non-allergic rhinitis may be a presenting complaint for systemic disorders such as granulomatous or eosinophilic polyangiitis, and sarcoidoisis. Infective rhinitis can be caused by viruses, and less commonly by bacteria, fungi and protozoa.

Macrophage polarisation affects their regulation of trophoblast behaviour.

INTRODUCTION: During the first trimester of human pregnancy, fetally-derived extravillous trophoblast (EVT) invade into the uterine decidua and remodel the uterine spiral arteries to ensure that sufficient blood reaches the maternal-fetal interface. Decidual macrophages have been implicated in the regulation of decidual remodelling, and aberrant activation of these immune cells is associated with pre-eclampsia. METHODS: The monocytic cell line THP-1 was activated to induce a classically- or alternatively-activated macrophage phenotype and the conditioned media was used to treat the EVT cell line SGHPL-4 in order to determine the effect of macrophage polarisation on trophoblast behaviour in-vitro. SGHPL-4 cell functions were assessed using time-lapse microscopy, endothelial-like tube formation assays, and western blot. RESULTS: The polarisation state of the THP-1 cells was found to differentially alter the behaviour of trophoblast cells in-vitro with pro-inflammatory classically-activated macrophage conditioned media significantly inhibiting trophoblast motility, impeding trophoblast tube formation, and inducing trophoblast expression of cleaved caspase 3, when compared to anti-inflammatory alternatively-activated macrophage conditioned media. DISCUSSION: Macrophages can regulate trophoblast functions that are critical during decidual remodelling in early pregnancy. Importantly, there is differential regulation of trophoblast function in response to the polarisation state of these cells. Our studies indicate that the balance between a pro- and anti-inflammatory environment is important in regulating the cellular interactions at the maternal-fetal interface and that disturbances in this balance likely contribute to pregnancy disorders associated with poor trophoblast invasion and vessel remodelling.

Minimising the risk of prion transmission by contact tonometry.

AIMS: The unknown prevalence of variant Creutzfeldt-Jakob disease (vCJD) in the UK population has led to fears of horizontal transmission through routine medical procedures. The potential risk of transmission via contact tonometry was examined. METHODS: The total amount of protein carried over by tonometer tips after applanation of patients was assessed. RESULTS: Tonometer tips had an inherent ability to carry proteinaceous material. There was a large variability in the load carried over between individual patients. Rinsing tonometer tips in water reduced protein carryover. Wiping the tonometer tips also reduced carriage, though less dramatically. CONCLUSION: There is a small theoretical risk of transmission of vCJD by contact tonometry through reuse, but this should be reduced if the prisms are washed and wiped. In the light of these findings a protocol for the management of reusable tonometer prisms is recommended.

Systemic cyclosporin A in high risk penetrating keratoplasties: a case-control study.

AIM: To examine the efficacy of systemic cyclosporin A (CSA) in preventing rejection and graft failure in high risk keratoplasty (PK). METHODS: A retrospective case-control study with 49 patients in both the CSA group and the control group. The patients receiving CSA were at high risk of graft rejection and failure. Controls were identified from surgical audit books and had high risk characteristics. RESULTS: There was no statistical difference in preoperative risk factors and the use of postoperative topical steroids between the two groups. The median follow up in the CSA group was 22 months and 27 months in the control group. One or more rejection episodes occurred in 18 out of 49 (36.7%) cases in the CSA group and 26 out of 49 (53.1%) in the control group. Graft failure from all causes occurred in 16 (32.7%) CSA patients and 18 (36.7%) control patients. Four (8.2%) of the CSA group compared to eight (16.3%) in the control group failed because of rejection. 22 (44.9%) out of 49 patients in the CSA group had side effects. In five (10.2%) patients, CSA was stopped because of the side effects; eight patients had elevated serum urea and creatinine and four developed hypertension. Minor side effects reported include gum hyperplasia, increased sweating, backache, nausea, feeling unwell, oral candidiasis, cramps, and paraesthesia of the extremities. CONCLUSION: These results suggest that the benefit of CSA over conventional therapy in preventing rejection episodes and subsequent graft failure is only moderate and did not reach statistically significant levels in this study. Considering the high frequency of side effects and the cost of CSA, a randomised control trial may be necessary to determine the true value of CSA in high risk penetrating keratoplasty.

Scleral contact lenses for overnight wear in the management of ocular surface disorders.

PURPOSE: To describe the use of overnight wear scleral contact lenses (Scl CLs). The authors describe 7 patients using this modality of contact lens wear. Most of the lenses were made from highly gas-permeable materials, but a long-standing case is also reported when the lenses were made from PMMA, which is impermeable to gases. BACKGROUND: There is a range of therapeutic indications for the use of Scl CLs. The development of rigid gas-permeable (RGP) materials has widened this range. CASE REPORTS: Seven case reports are presented which describe patients in whom severe ocular surface disease has been managed with overnight-wear Scl CLs. The indications were: corneal exposure, post-radiotherapy complications, Stevens Johnson disease, recurrent erosion and congenital or post-surgical lid defects. CONCLUSION: Scl CLs provide a therapeutic option for a range of complicated corneal and ocular surface conditions for which the treatment by other methods is either unsuitable or less effective. They have several advantages over silicone rubber and hydrogel lenses. The relative ease of handling for some patients allows removal for cleaning, their rigidity gives stability and a high degree of protection to the ocular surface, and the presence of a pre-corneal fluid reservoir optically neutralises an irregular corneal surface. Highly oxygen-permeable materials enable consideration of overnight wear in appropriate circumstances.

Cytokine production and mRNA expression by conjunctival T-cell lines in chronic allergic eye disease.

BACKGROUND: Activated CD4+ T cells, mast cells and eosinophils are the main cytokine-producing cell-types infiltrating the conjunctiva during chronic allergic eye diseases. Interactions between these cells are thought to play an important immunopathogenic role in these disorders (giant papillary conjunctivitis; vernal keratoconjunctivitis; atopic keratoconjunctivitis). OBJECTIVE: The objective was to compare the cytokine profiles of conjunctival T-cell lines from patients with different forms of chronic allergic eye disease. METHODS: T cells were isolated from conjunctival biopsies and non-specifically expanded into lines. The lines were immunophenotyped by flow cytometry. Cytokine production was quantified by immunoassays and more sensitive molecular techniques were used to investigate cytokine mRNA expression to identify the presence of interleukin (IL) -2, IL-4 and interferon (IFN) -gamma transcripts. RESULTS: Following four to six rounds of stimulation, the conjunctival T-cell populations were CD3+ (> 93%), with variable levels of CD4 and CD8 expression. All were HLA-DR+ (> 80%) with some HLA-DQ expression. Conjunctival T-cell lines from atopic keratoconjunctivitis produced selective increases in IFN-gamma, IL-10 and IL-13 (P<0.01), those from vernal keratoconjunctivitis produced increased IL-5 (P<0.01) whereas T-cell lines from giant papillary conjunctivitis produced only low levels of cytokines. IL-4 was only detected at the mRNA level and was expressed in four out of five T-cell lines in the vernal keratoconjunctivitis group. In contrast there was moderate to strong expression of IFN-gamma in five out of six T-cell lines in atopic keratoconjunctivitis. CONCLUSION: Different patterns of T-cell cytokine profiles were observed for each disease, with low-level, non-polarized cytokine production in giant papillary conjunctivitis, a TH2-like profile in vernal keratoconjunctivitis and a shift towards a TH1-like profile in atopic keratoconjunctivitis.

The immunomodulatory effect of topical cyclosporin A in atopic keratoconjunctivitis.

PURPOSE: To perform a detailed examination of the immunomodulatory effects of topical cyclosporin A (CsA) in conjunctival tissue from patients with atopic keratoconjunctivitis (AKC). METHODS: Patients with active AKC were randomly allocated into two groups of four patients. For 3 months one group received 2% CsA drops, and the other group received placebo drops. Superior tarsal conjunctival biopsy specimens were harvested before and after treatment and examined by one- and two-color immunohistochemistry to compare leukocyte counts, HLA-DR+ and IL-2R+ cell counts, HLA-DR positivity of conjunctival epithelial cells, and counts of T cells expressing the cytokines interleukin (IL)-2, IL-3, IL-4, IL-5, and interferon (IFN)-gamma. RESULTS: Posttreatment values were significantly less than pretreatment values for the total number of leukocytes and in the numbers of CD3+ T cells, CD4+ cells, CD8+ cells, CD20+ B cells, neutrophils, and macrophages, and there was a decrease in the CD4-CD8 ratio (P = 0.03) in the CsA group. There was a reduction from before CsA treatment to after CsA-treatment in the numbers of HLA-DR+ and IL-2R+ cells (P = 0.03), but the reduction in the epithelial cell HLA-DR expression did not reach significance. The number of T cells staining for IL-3 and IL-5 was reduced, although not to statistical significance, but there was a significant reduction in the number of T cells expressing IL-2 and IFN-gamma (P = 0.03) after CsA treatment compared with initial values. There were no statistically significant differences between pretreatment and posttreatment values in the placebo group. There was a clinical improvement in the CsA group and a clinical worsening in the placebo group. CONCLUSIONS: The in vitro effects of CsA translate into a reduction in T cells, a normalization of the CD4-CD8 ratio, a decrease in T-cell activation, and a reduction in T-cell cytokine expression, especially IL-2 and IFN-gamma. The decrease in HLA-DR expression may be mediated by the change in IFN-gamma. There were fewer B cells but not fewer plasma cells after CsA and no change in IL-4 expression, suggesting minimal effects on type I hypersensitivity responses. There was no significant reduction in mast cell or eosinophil numbers, but direct effects of topical CsA on their function may play a role in the therapy of ocular allergic disease. These results show that the beneficial effects of topical CsA in AKC are accompanied by important changes in conjunctival immune cell profiles.

Eosinophil surface antigen expression and cytokine production vary in different ocular allergic diseases.

BACKGROUND: The pathophysiology of chronic ocular allergic disease is not well understood. An eosinophil infiltrate is characteristic of such disease and eosinophil activity can be related to disease severity and to keratopathy, the most serious complication. Recently, eosinophils have been shown capable of cytokine production, particularly in allergic disease, although the disease-specific cytokine spectrum of tissue eosinophils is unknown. OBJECTIVES: We sought to determine eosinophil numbers (absolute numbers and percentage of total leukocytes), cell surface antigen expression, and cytokine production in conjunctiva in chronic allergic eye disease and their relationship to corneal involvement. METHODS: Ultrathin sections of conjunctiva were examined by tissue staining and by 1- and 2-color immunohistochemistry. RESULTS: Eosinophil numbers were greater in giant papillary conjunctivitis (GPC) and vernal keratoconjunctivitis (VKC) and not related to corneal involvement. The eosinophil expression of the cell surface antigens intercellular adhesion molecule-1, CD4, IL-2R, and HLA-DR was greater in atopic keratoconjunctivitis (AKC) and VKC, the disorders with corneal disease, than in GPC, in which the cornea is not involved. For most cytokines, localization to eosinophils was greater for VKC and AKC than for GPC. RANTES, TGF-beta, and TNF-alpha localized to eosinophils in all disorders. Variations in the pattern of eosinophil-cytokine localization were found. In VKC IL-3, IL-5, IL-6, and GM-CSF were prominent; in GPC IL-5 was prominent; and in AKC IL-4, IL-8, and GM-CSF were prominent. CONCLUSIONS: Chronic ocular allergic disorders affecting the cornea are distinguished from disorders that do not do so by greater expression of eosinophil surface antigens (which may imply greater cell activation) and differences in cytokine localization to eosinophils. These differences may be secondary to the variations in T-cell subsets or a primary phenomenon. Changes in eosinophil function, rather than cell numbers, may be important in clinical variations, such as keratopathy, and may allow future therapeutic exploitation.

A randomized, placebo-controlled trial of topical cyclosporin A in steroid-dependent atopic keratoconjunctivitis.

OBJECTIVE: This study aimed to investigate the therapeutic effect of topical cyclosporin A (CsA) 2% in maize oil as a steroid-sparing agent in steroid-dependent atopic keratoconjunctivitis. DESIGN: Prospective, randomized, double-masked, placebo-controlled trial. PARTICIPANTS: Twenty-one patients with steroid-dependent atopic keratoconjunctivitis were studied. INTERVENTION: Patients used either topical CsA or vehicle four times daily for 3 months in addition to their usual therapy, and the clinical response was used to taper or stop topical steroids when possible. MAIN OUTCOME MEASURES: Steroid drop usage per week, ability to cease steroid use, scores for symptoms and clinical signs, drop side effects, and overall subjective rating of trial drop by patients and clinician were measured. RESULTS: Cyclosporin A had a greater steroid-sparing effect than did placebo. Nine of 12 CsA patients ceased steroids compared to 1 of 9 placebo patients (P = 0.01), the final steroid use was lower in the CsA group (2.6 +/- 1.4 vs. 27.7 +/- 17.7, P = 0.005), and the mean reduction in steroid use was greater for CsA (85.5 +/- 14.7 vs. 13.9 +/- 16.0, P = 0.005). Clinical signs and symptom scores were reduced to a greater level for CsA. Serious side effects were lid skin maceration in one patient using CsA and an allergic reaction in one placebo patient. Marked blurring of vision after drop instillation was common in both groups, but intense stinging was more common in CsA patients (9/12 vs. 1/9, P = 0.01), limiting frequency of drop use. The clinician rated the trial drops as good or excellent more frequently for CsA (11/12 vs. 0/9, P < 0.0001). CONCLUSIONS: Topical CsA is an effective and safe steroid-sparing agent in atopic keratoconjunctivitis and, despite difficulties in patient tolerance, also improves symptoms and signs.

The role of conjunctival epithelial cells in chronic ocular allergic disease.

Recent evidence suggests that mucosal epithelial cells are capable of actively participating in immune reactions via expression of surface antigens, such as adhesion molecules, and synthesis of cytokines. This appears to be important in the pathophysiology of non-ocular allergic disorders. The objectives of the experiments were to compare the expression of HLA-DR, ICAM-I and pro-allergic cytokines in conjunctival epithelial cells in the different chronic ocular allergic disorders with each other and with normal subjects. Conjunctiva from normal patients (n=10) and patients with vernal keratoconjunctivitis (VKC, n=10), atopic keratoconjunctivitis (AKC, n=10) and contact lens-associated giant papillary conjunctivitis (GPC, n=10) were examined by immunohistochemistry. Epithelial cell staining for surface antigens and cytokines was graded by one masked observer using a four point scale based on the percentage of epithelial cells staining positive. There was no expression of ICAM-1 or HLA-DR in the normal conjunctival epithelial cells, but both antigens were induced on conjunctival epithelial cells in the allergic tissue, and there was greater expression in AKC and VKC compared with GPC. Cytokines IL-6, IL-8, RANTES and TNF-alphaall localised to normal conjunctival epithelial cells. RANTES was upregulated in all the allergic disorders and IL-8 was upregulated in GPC. IL-3 and GM-CSF were not expressed in normal conjunctival epithelial cells. GM-CSF was expressed in all disorders and there was greater expression in AKC compared with GPC and VKC. IL-3 was expressed only in AKC and VKC epithelial cells. These results suggest that conjunctival epithelial cells play an important pro-inflammatory role in chronic ocular allergic diseases; ICAM-1 may allow epithelial cells to recruit, retain and locally concentrate leukocytes; the presence of HLA-DR raises the question of conjunctival epithelial cell antigen presentation. The epithelial cytokines which are upregulated are known to promote eosinophilic inflammation and are typical of allergic inflammation. The differences in cytokine patterns may be exploitable for future therapy.

Allergic eye disease--a clinical challenge.

Currently, six basic allergic eye diseases are recognized. In seasonal (SAC) and perennial allergic conjunctivitis (PAC), the allergic response is mediated predominantly by mast cells, whereas the more severe conditions, vernal (VKC) and atopic keratoconjunctivitis (AKC) and giant papillary conjunctivitis (GPC), are associated with a preponderance of T cells. Acute allergic conjunctivitis (AAC) occurs when a large quantity of allergen inoculates the eye and is usually self-limiting. SAC, the most common ocular allergy, is the ocular component of hayfever. PAC in the UK is most commonly caused by the house-dust mite (HDM); diagnosis is confirmed by skin-prick tests, eosinophils in the conjunctival smear, and raised tear or serum total IgE. SAC and PAC can usually be managed with chromone eyedrops and antihistamines. VKC usually presents in children under 10 years of age and mainly affects boys. Sufferers frequently have a personal or family history of atopy. Corneal involvement can occur in VKC, making it potentially sight-threatening. AKC occurs in atopic adults, and like VKC it affects the cornea. VKC and AKC require steroid treatment under specialist supervision; minimization of the steroid dose can often be achieved with use of a chromone. GPC occurs due to repeated contact of the conjunctival surface with a foreign surface, such as contact lenses. Attention to lens hygiene or switching to different lenses and treatment with a chromone are frequently effective. In all allergic eye diseases contact with the precipitating allergen should be avoided as far as possible.

A study of 530 patients referred for rigid gas permeable scleral contact lens assessment.

PURPOSE: The purpose of this study was to analyse the current application of scleral contact lenses in two specialist centres. METHODS: The case notes of 530 patients assessed for fitting or refitting with rigid gas permeable (RGP) scleral lenses were retrospectively analysed to determine the indication for contact lenses and the outcome. Scleral lenses had been offered as a conservative management option in suitable cases for a variety of visual and medical indications. RESULTS: Various types of primary corneal ectasia, ranging from low grade to advanced, including keratoconus, keratoglobus, and pellucid marginal degeneration, formed 53.0% of the total referred for assessment. The other principal indications for contact lenses were corneal transplant (15.8%), aphakia (10.3%), high myopia (8.9%), and various ocular surface disorders (8.2%). Sixty percent continued to use scleral lenses, 42.9% RGP, and 17.1% polymethylmethacrylate lenses. Twenty-two percent discontinued scleral lens wear or failed a trial of scleral lenses, with 9.3% in progress at the time of assessment and 8.7% lost to follow-up. CONCLUSIONS: In the authors' opinion, scleral lenses have retained their traditional role in the management of complex ametropia and ocular surface disease. That role has been further enhanced by the application of gas permeable materials.

Fourier transform analysis of human corneal endothelial specular photomicrographs.

Fourier analysis of in vivo human corneal endothelial cell structure was investigated using specular photomicrographs for a range of ages from less than one year to over 70. The theoretical basis for this analysis was investigated using mathematical models of cell structures where the elements determining their form could be modified in a controlled and quantified manner. The resulting Fourier transform properties were related to properties of cell structure. The experimental factors underlying this analysis were then studied using digitized images of corneal endothelial cells. It was found that the Fourier transforms provided quantitative descriptions of population cell size and organisation. For the smaller, more regular cell structure from the younger eyes, the expected larger rings of the Fourier transforms were demonstrated. Specular photomicrographs of older eyes gave rise to smaller diameter rings in their Fourier transforms. These results are consistent with the previous studies which used manual tracings of human endothelial cell patterns. This is the first demonstration of the direct Fourier analysis of clinical human corneal specular photomicrographs.

T-cell cytokines in chronic allergic eye disease.

BACKGROUND: The pathophysiology of chronic allergic eye disease cannot be explained by type I hypersensitivity alone, and T cell-mediated inflammation has been strongly implicated as a possible additional mechanism. Previous studies suggested that T(H2)-like T cells play an important role in one form of chronic allergic eye disease. OBJECTIVES: This study examined the cytokine profile of T cells in different clinical groups of subjects with chronic allergic eye disease (i.e., vernal keratoconjunctivitis [VKC], atopic keratoconjunctivitis [AKC], and giant papillary conjunctivitis [GPC]) and normal control subjects. METHODS: In situ hybridization was used to identify cytokine messenger RNA (mRNA), and two-color immunohistochemical analysis was used to demonstrate cytokine immunoreactivity localizing to T cells in the conjunctiva. RESULTS: Allergic tissue expressed increased levels of mRNA for IL-3, IL-4, and IL-5 when compared with normal tissue. There was significantly greater IL-2 mRNA expression in subjects with AKC than in those with VKC (p = 0.004) and those with GPC (p = 0.02). Immunoreactivity for T-cell IL-5 was present more frequently in subjects with VKC (p = 0.004), GPC (p = 0.02), and AKC (p = 0.04) than in normal control subjects. However, T-cell IFN-gamma protein expression was greater in subjects with AKC than in subjects with VKC (p = 0.01), GPC (p = 0.01), and control subjects (p = 0.005). CONCLUSIONS: These results show a T(H2)-like T-cell cytokine array in subjects with VKC and GPC but a shift in cytokine profile toward a T(H1)-like pattern, potentially because of differences in chronicity of the disorders, in subjects with AKC. These important functional T-cell variations in chronic allergic eye conditions are likely to be important in understanding differences in clinical characteristics and therapeutic responses.

Comparative intraocular penetration of topical and injected cefuroxime.

AIMS: The choice of a prophylactic antibiotic for cataract surgery is dependent on its antibacterial activity and tissue penetration. The influence of the route and timing of administration of cefuroxime on its intraocular concentrations was examined. METHODS: 120 patients were recruited before cataract surgery into a prospective trial to compare the anterior chamber concentration of cefuroxime at a fixed time after administration by three routes. In a further 110 patients, the interval before sampling was varied in order to permit an examination of the kinetics of penetration. In another 10 patients, cefuroxime was given topically at the completion of surgery to assess the effect of a corneal wound on aqueous penetration. Cefuroxime concentrations were measured by high performance liquid chromatography on 0.2 ml samples of aqueous aspirated from the anterior chamber. Mean aqueous concentrations of cefuroxime for each group were compared using Student's t test. RESULTS: After 25 mg cefuroxime, mean aqueous concentrations increased in the order forniceal (< 0.1 microgram/ml) < topical (0.18 microgram/ml) < subconjunctival (2.31 microgram/ml) when sampled 12-24 minutes after administration. Aqueous concentrations of cefuroxime reached a peak between 80 and 110 minutes after both forniceal and peribulbar injection but were still rising at this time after subconjunctival injection. Topical application of 12.5 mg cefuroxime to eyes with a 10 mm corneal wound resulted in a mean aqueous concentration of 9.34 micrograms/ml. CONCLUSION: In the intact eye, only sub-conjunctival injection resulted in clinically significant aqueous concentrations of cefuroxime (> 1 microgram/ml) between 12 and 24 minutes after administration. For all routes, maximal aqueous concentrations were delayed by at least 80 minutes from administration. In the presence of a corneal wound, high aqueous levels of cefuroxime were rapidly attained after topical application.

Ocular chloramphenicol and aplastic anaemia. Is there a link?

The question of a link between the use of topical ocular chloramphenicol and the incidence of aplastic anaemia continues to be a controversial issue in ophthalmological spheres. At present topical ocular chloramphenicol is widely used in the UK for the treatment of conjunctivitis, whereas it is very rarely prescribed for this indication in the U.S. Individual policies vary around the rest of the world. The evidence for and against any association between topical and ocular chloramphenicol and an increased risk of aplastic anaemia is reviewed, and the reasons behind the current prescribing policies are clarified. The discussion generated in the literature over the past 2 years over this issue is considered, along with the published debate from the past 3 decades. The debate is not conclusive, but by presenting or referencing the specific case reports and the published opinions of various experts, we hope to enable the reader to make his or her own informed decision as to whether use of the topical preparation of chloramphenicol should be considered by the ophthalmological community.

Limbal transplantation.

BACKGROUND: Limbal transplantation is a surgical technique of ocular surface epithelial transplantation advocated for a variety of ocular surface disorders with presumed stem-cell deficiency. Limbal transplantation was performed in 18 patients with ocular surface disease, which included aniridia keratopathy, chronic contact lens-associated epitheliopathy, chemical injury, Stevens-Johnson syndrome, and corneal intraepithelial dysplasia. METHODS: Limbal allograft transplantation was performed in nine eyes with the use of heterologous limbal tissue from cadaveric donor eyes or live relatives, whereas nine eyes underwent conventional limbal autograft transplantation. RESULTS: Limbal allograft transplantation resulted in restoration of a stable ocular surface in seven of nine cases, with early visual rehabilitation and significant reduction in symptoms. At a mean follow-up period of 14.7 months, one patient was noted to have failure of the inferior graft related to postoperative microbial keratitis, whereas one patient had acute rejection episode after early cessation of oral cyclosporine. The mean follow-up period for limbal autografts was 27.1 months. Limbal autograft failure occurred in two patients with limbal autograft transplantation for chronic contact lens-associated epitheliopathy. One contact lens wearer had epithelial dysplasia in the fellow eye at the previous donor site. Subclinical involvement of the fellow eye is suggested as a reason for graft failure and donor eye complications in these eyes. CONCLUSIONS: Although it requires a longer follow-up period, limbal allograft transplantation is a viable procedure for bilateral ocular surface disease and for presumed bilateral disease (viz bilateral exposure to injurious agents) and may be a preferred alternative to limbal autograft transplantation for such patients. The role of immunosuppression is being evaluated.