Alan Ridgway

Diurnal variations in human corneal thickness.

AIM: To elucidate the diurnal variation in human corneal thickness over a 48 hour period. METHOD: Changes in central corneal thickness were monitored in eight healthy subjects (four male, four female) aged between 10 and 63 years using an ultrasonic pachymeter. Measurements were made over a 48 hour period-immediately before sleep, immediately upon waking and at 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3 hours, and at 2 hour intervals thereafter throughout the remainder of each day. RESULTS: The mean corneal thickness for the group (SD) was 546 (14) microns, with a mean overnight increase of 5.5% (2.9%) (range 1.9-12.6%) and a maximum diurnal increase of 7.2% (2.8%) (range 2.1-14.3%). Individual differences in the extent of diurnal and overnight variation occurred within the group. For three subjects, the first reading taken on waking was not the highest and corneal thickness continued to increase. CONCLUSION: These data confirm an increase of corneal thickness during sleep, but also reveal considerable variation during waking hours. Thus, the overnight changes in corneal thickness are not truly representative of diurnal variations in human corneal thickness and, in fact, much greater diurnal variation occurs than the 3.0-4.4% previously reported.

A mutation in the RIEG1 gene associated with Peters’ anomaly

Mutations within the RIEG1 homeobox gene on chromosome 4q25 have previously been reported in association with Rieger syndrome. We report a 3′ splice site mutation within the 3rd intron of the RIEG1 gene which is associated with unilateral Peters’ anomaly. The mutation is a single base substition of A to T at the invariant -2 site of the 3′ splice site. Peters’ anomaly, which is characterised by ocular anterior segment dysgenesis and central corneal opacification, is distinct from Rieger anomaly. This is the first description of a RIEG1 mutation associated with Peters’ anomaly.

Successful medical therapy of Acanthamoeba keratitis with topical chlorhexidine and propamidine

Introduction. Following laboratory studies on new potential chemotherapy for Acanthamoeba keratitis, when chlorhexidine and propamidine provided an additive in vitro effect, a series of 12 patients with culture-proven Acanthamoeba keratitis from three UK centres was monitored during and after therapy.Methods. In all cases the clinical diagnosis was confirmed by amoebal culture. In some instances identification of the protozoa by direct microscopy of corneal tissue was possible. The medication was provided topically in drop form until the keratitis had resolved. In vitro sensitivity to chlorhexidine and propamidine was performed on all isolates and compared with sensitivity to a range of other drugs used for treatment of the infection.Results. In vitro drug testing confirmed that trophozoites and cysts of all 12 Acanthamoeba isolates were fully sensitive to chlorhexidine and propamidine. Therapy was satisfactory for controlling and eradicating the acanthamoebal infection in all patients. Three patients developed discrete stromal infiltration at the site of infection that resolved 1 week after commencing therapy, with or without use of steroids. Two patients developed a late inflammatory effect in the stromal scar at 6 months, which resolved with steroids. No clinical evidence of chlorhexidine toxicity was found in any patient.Conclusions. The combination of topical chlorhexidine and propamidine was very effective for treating Acanthamoeba keratitis provided the drugs were continued for a sufficient period. No drug toxicity or resistance of Acanthamoeba isolates was observed in the 12 treated patients.

Heterogeneity in granular corneal dystrophy: Identification of three causative mutations in the TGFBI (BIGH3) gene—Lessons for corneal amyloidogenesis †

Six autosomal dominant corneal dystrophies are caussed by mutations in the TGFBI (BIGH3) gene on chromosome 5q31: three types of lattice corneal dystrophy (LCD), including type I and type IIIA, granular, Avellino (ACD), and Reis‐Bucklers. Initially an exact genotype‐phenotype correlation was reported. We report three families, with differing clinical features, all presenting with “granular” corneal dystrophy. We analysed the TGFBI gene by SSCP analysis and direct sequencing in order to further assess the genotype‐phenotype correlation. We describe three separate mutations in TGFBI: one novel, one initially described as causing ACD, and one previously described. The novel mutation, R124S, is at the identical position to the mutation causing LCD type I (CDL1). We review the clinical and histological phenotypes of the corneal dystrophies and hypothesize that the ability of a mutation to cause amyloid deposition depends on the location and nature of the mutation. In addition, we suggest that the classification of the granular corneal dystrophies be revised according to mutation type and that ACD should not be classified as a distinct morphological entity. Hum Mutat 14:126–132, 1999.

Visual function after penetrating keratoplasty for keratoconus: a prospective longitudinal evaluation

AIMS To evaluate visual function and vision specific health status in patients undergoing penetrating keratoplasty for keratoconus. METHODS A prospective longitudinal study measuring logMAR visual acuity, contrast sensitivity, disability glare, binocular visual field, stereoacuity, and subjective visual function (VF-14) was conducted on 18 patients with keratoconus undergoing penetrating keratoplasty (PK), including six patients who had already had PK in the fellow eye. Data were collected preoperatively and at 3, 9, and 18 months after surgery. RESULTS Within 3 months of surgery there was significant improvement in aided visual acuity, contrast sensitivity, and stereoacuity (p<0.05); disability glare (p<0.05) no longer had a significant detrimental effect on these variables. VF-14 score improved significantly throughout the postoperative period (p<0.05). There was significant correlation of the VF-14 score with aided visual acuity, binocular visual field, and stereoacuity. Postoperative astigmatism (<4Dv >4D) did not affect the VF-14 score significantly. CONCLUSIONS There is substantial and rapid improvement in visual function and vision specific health status in keratoconic patients as a result of uncomplicated penetrating keratoplasty.

Macular corneal dystrophy: reduction in both corneal thickness and collagen interfibrillar spacing

The interfibrillar spacing of collagen fibrils was measured at twenty different positions across a macular dystrophy cornea using synchrotron X-ray diffraction. Unlike previous work of this type the cornea had not been frozen for storage. The spacings were all significantly lower than the spacings which existed at similar positions across a normal adult human cornea. This close-packing of collagen fibrils seems to be responsible for the reduced thickness of the central cornea in macular dystrophy. Neither the patients serum or corneal tissue contained appreciable amounts of sulfated keratan sulfate, this classifies the disease as Type I macular corneal dystrophy.

Prediction of refractive outcome in penetrating keratoplasty for keratoconus.

We carried out a retrospective study to evaluate the relationship between vitreous cavity length, graft size, and final spherical equivalent refraction after penetrating keratoplasty (PK) for keratoconus. We found a straight-line relationship between vitreous cavity length and spherical equivalent for a one-surgeon series using the same technique throughout. The use of 0.25-mm undersized grafts shifted the results an average of 2.2 Dioptres in a more hypermetropic direction (p = 0.07 for the whole group, p < 0.01 for paired eyes). Hence the final spherical equivalent following PK for keratoconus can be predicted. Also, by altering the size of the donor graft button, the final refraction can be manipulated to some extent towards acceptable ametropia or to match the refraction of the fellow eye.

Management of pellucid marginal corneal degeneration

Purpose A retrospective study to ascertain the management of pellucid marginal corneal degeneration (PMCD).Method and results Sixteen patients (average age 42.6 years) presented with PMCD. PMCD was bilateral in 13 and unilateral in 3 patients. Eight eyes underwent surgery. Nineteen eyes were managed non-surgically. Surgery involved corneal wedge excision (WE) (6 eyes), penetrating keratoplasty (PK) (3 eyes) and lamellar thermo-keratoplasty (LTK) (1 eye). Immediate pre-operative average visual acuity (VA) was 6/24, 6/10 and 6/60 with an average pre-operative astigmatism of 11.40 D, 9.75 D and 20.5 D for WE, PK and LTK respectively. After an average post-operative follow-up of 57 months, 66 months and 1 year, the average astigmatism was 8.90 D, 4.63 D and 6.00 D with an average final VA of 6/19, 6/15 and 6/6 for WE, PK and LTK respectively. In the nonsurgical group, at presentation, 40% of eyes had a VA of 6/12 or better. After an average follow-up period of 32.3 months, 80% of eyes had a visual acuity of 6/12 or better. Optical correction was achieved with spectacles and or contact lenses.Conclusions Surgical correction for PMCD provides poor long-term reduction of astigmatism. Patients with PMCD may be adequately corrected in the long term by the use of scleral fitted gas-permeable contact lenses.

Lectin binding sites in normal, scarred, and lattice dystrophy corneas

Normal, scarred, and dystrophic corneas were histochemically probed with a panel of 16 lectins by means of an avidin-biotin revealing system. Normal corneal epithelial cells, keratocytes, and endothelial cells expressed at least two distinct N-linked oligosaccharide subsets, of the non-bisected, biantennary and bisected, bi-/triantennary types. Corneal scars stained variably with the lectin subsets described above, and with Maclura pomifera agglutinin. Lattice dystrophy corneas showed a loss of the oligosaccharide expression observed on the plasma membranes of normal epithelial cells, and there was concurrent deposition of extracellular glycoprotein within the corneal stroma, which was of the same oligosaccharide subsets as were lost from the epithelial cell plasma membranes. This extracellular stromal glycoprotein was far more widely deposited than the amyloid and extended well beyond the stromal scarring. We propose that these observations are related and that in lattice corneal dystrophy a glycoprotein(s) is shed from the plasma membranes of epithelial cells and sequestrated within the corneal stroma, where it subsequently stimulates amyloid deposition.

Penetrating keratoplasty for pseudophakic corneal oedema.

AIMS--The study was designed to investigate the results of penetrating keratoplasty (PK) for pseudophakic corneal oedema (PCO). METHODS--Retrospective analysis of 80 consecutive patients (82 eyes) who underwent PK for PCO between the years 1980-1992 with a minimum follow up of 12 months. RESULTS--PKs for PCO have accounted for as many as 20% of all grafts performed in the hospital in recent years. The interval between cataract extraction and PK ranged from 6 to 161 months (mean 51 months). The intraocular lens was removed in 45 (55%), left in situ in 30 (37%), and exchanged in seven (8%) of cases respectively. Of the intraocular lenses involved 62% were iris supported, 31% angle supported, and 7% were posterior chamber lenses. Actuarial analysis shows graft survival to be 91% at 1 year and 86% at 2 years after surgery. The likelihood of graft survival was significantly enhanced by removal of the intraocular lens (p < 0.01). A corrected Snellen visual acuity worse than 6/60 was present in 36% of patients with a clear corneal graft. Ocular comfort was achieved in all patients with a clear corneal graft. CONCLUSION--PK for PCO resulted in a disappointing visual result in a large proportion of patients. PK was, however, successful in relieving pain and corneal ulceration when present.