Roger J. Buckley

Prognostic Factors for the Progression of Keratoconus

PURPOSE The progression of keratoconus to a stage where penetrating keratoplasty (PK) is required for visual rehabilitation has considerable implications for affected patients. To assist with counselling, the authors have attempted to identify which factors measurable early in the course of the disease may indicate the likelihood of subsequent surgery. METHODS The authors reviewed the records of all patients who attended a single center over a 7-year period for contact lens management of their keratoconus. The influence of clinical variables on the time taken for the worst eye to progress to PK was evaluated by actuarial methods and multivariate analysis. RESULTS Included in the study were 2723 patients with a mean follow-up for unoperated eyes from the first visit of 4.5 years (range, 3 months to 28 years). Data were available for multivariate analysis in 2363 patients. At the end of the study period, 757 eyes (21.6% of all patients) had been grafted. The number of eyes progressing to PK was independently related to both the maximum and minimum keratometry, a corneal cylinder of more than 1.9 mm, the Snellen acuity, the racial group (P < 0.0001), and the age at presentation (P = 0.0006). Sex, laterality, systemic atopic disease, maternal or paternal age at birth, joint hypermobility, and a family history of keratoconus were not statistically related to outcome. Progression to PK in one eye increased the risk of progression in the contralateral eye (P < 0.0001) and a linear model of disease progression is proposed. CONCLUSIONS Several clinical variables can be measured in patients at the presentation of keratoconus that influence the probability of a subsequent PK.

Clinical Features of Atopic Keratoconjunctivitis

The clinical spectrum of ocular disease in 37 patients with atopic keratoconjunctivitis (AKC) is described. Patients typically had a severe blepharoconjunctivitis. Associated corneal scarring, suppurative keratitis, or keratoconus were the major causes of visual loss. Serum and tear samples from these patients were analyzed to quantify total and specific IgE antibodies. The results were compared as a case control study with results from samples from 55 patients with other forms of atopic disease and 16 nonatopic volunteers. Although the mean values for total and specific IgEs in the serum of patients with atopic disease were markedly higher than the values from nonatopic controls (P less than 0.00002), a difference between the disease groups could not be demonstrated (P greater than 0.05). There were also differences between both the total IgE (P = 0.0002) and pollen-specific IgE (P = 0.015) in tears from patients with atopic disease and nonatopic controls, but not for house dust mite or cat dander-specific IgEs. These results suggest that clinical differences between groups of patients with chronic allergic external eye disease are not associated with specific patterns of IgE production.

Limbal transplantation in the management of chronic contact-lens-associated epitheliopathy

We describe the clinical management of 6 patients who developed a chronic corneal epitheliopathy 1–18 years after commencing soft contact lens wear. All had a history of exposure to thiomersal in contact lens fluids. The corneal changes were characterised by epithelial haze and superficial stromal vascularisation which extended from the limbus towards the visual axis. Five patients were observed for a minimum of 18 months after stopping contact lens wear before undergoing limbal transplantation. A good result was obtained in 1 patient who had worn a contact lens in one eye only. Recurrent epithelial changes were observed on the recipient eyes of the remaining patients who had previously worn contact lenses bilaterally, and in 1 patient epithelial haze also developed adjacent to the donor site in the previously clinically normal donor eye. All 5 patients experienced an improvement in symptoms post-operatively but in 2 patients the visual acuity later deteriorated because of epithelial irregularity. The sixth patient has not had surgery. We conclude that limbal stem cell dysfunction in chronic contact-lens-associated epitheliopathy may be subclinical and that autograft transplantation in bilaterally exposed patients may fail to restore the epithelial phenotype of the host eye whilst jeopardising the epithelial integrity of the donor eye by depleting its stem cell reserve.

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.

Acute Corneal Hydrops in Keratoconus

PURPOSE To determine the clinical factors associated with the development of acute corneal hydrops and its subsequent outcome. METHODS The authors identified 147 eyes (124 patients) with acute hydrops from a database of 5242 eyes (2723 patients) with keratoconus. They compared the clinical features of patients in whom hydrops developed with unaffected patients and assessed the progression to penetrating keratoplasty by actuarial methods. RESULTS Patients in whom acute hydrops developed tended to be younger males who had advanced corneal ectasia and a poor corrected Snellen visual acuity at the diagnosis of their keratoconus (P < 0.001). Acute hydrops also was more common in the presence of severe allergic eye disease (P < 0.001). The development of hydrops was a very significant risk factor for subsequently receiving a penetrating keratoplasty (P < 0.00001) and at the end of the study period 87 (59%) of the 147 eyes had surgery for visual rehabilitation. These eyes had a greater rate of graft rejection than eyes grafted without hydrops (P = 0.02). After resolution of the hydrops, 46 of the 60 unoperated eyes had been refitted with contact lenses, of which 28 (61%) achieved a Snellen visual acuity of 20/40 or better, although a better visual acuity often was present in the contralateral eye. Microbial keratitis developed in two of these eyes after refitting. CONCLUSIONS Although a penetrating keratoplasty often is indicated for visual rehabilitation after acute corneal hydrops, there is an increased rate of rejection. Only a minority of eyes were re-established in contact lenses after resolution of hydrops, but some patients achieved a functional level of visual acuity such that the procedure could be delayed or avoided.

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

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).

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.

Scleral contact lenses: the expanding role.

Purpose: The purpose of this study was to describe the current indications for scleral contact lens (ScCL) management at Moorfields Eye Hospital, London. Methods: A database of 1003 patients (1560 eyes) seen between September 1999 and May 2003, either assessed for an ScCL trial or to follow up previously issued lenses, was analyzed. Results: The major contact lens indication groups were keratoconus or other primary corneal ectasia (PCE), corneal transplant, and ocular surface disease (OSD). The 3 main small groups were aphakia, myopia, and ptosis. A total of 538 patients continued lens wear in 1 or both eyes, for a total of 808 eyes. The total numbers of eyes for each contact lens indication were PCE, 496 (61.4%); corneal transplant, 150 (18.6%); OSD, 91 (11.4%); aphakia, 17 (2.1%); myopia 21 (2.6%); ptosis 14 (1.7%); and a miscellaneous indication, 19 (2.2%). The percentages were similar to those of the total group of 1560 eyes. Seven hundred twenty lenses (89.1%) were rigid gas permeable (RGP), 708 were nonventilated, and 12 were fenestrated; 88 (10.9%) were ventilated polymethylmethacrylate or ptosis props. Conclusions: ScCLs continue to play a significant role in the management of corneal abnormalities, especially PCE, corneal transplant, and OSD. The great majority of lenses in use were nonventilated RGP designs.

Eosinophil granule major basic protein deposition in corneal ulcers associated with vernal keratoconjunctivitis

An indirect immunofluorescence assay detected eosinophil granule major basic protein in the inflammatory debris covering deepithelialized cornea in two patients with vernal keratoconjunctivitis. A slight degree of non-specific fluorescence was present in the control autopsy corneas. High concentrations of the eosinophil granule major basic protein inhibit epithelial migration and protein synthesis, whereas low concentrations affect epithelial migration. The results suggest participation of eosinophil granule major basic protein in the ulcerative process.

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.