Corneal repair following keratectomy. A comparison between conventional surgery and laser photoablation.

We have used the fluorescent dye dichlorotriazinyl aminofluorescein (DTAF) to demonstrate corneal remodeling following keratectomy in the rabbit. The dye was applied to the surface of 3.5 mm diameter anterior keratectomy wounds produced by either lamellar dissection or photoablation with an excimer laser (193 nm) to a depth of 15, 50 or 75 microns. Stromal wounds that had been ablated in 12 concentric steps to produce a graded profile with a central depth of 15 or 30 microns were also studied. The repair process was followed for periods of up to 6 months. These results were compared to wounds of similar dimensions in which an intrastromal keratectomy was performed and the anterior stromal surface replaced. Sections examined by fluorescence microscopy showed that connective tissue was deposited beneath the epithelium of all anterior keratectomy wounds irrespective of their mode of induction or depth. The deposition of this new tissue, and an associated thickening of the epithelium over the wound surface, appeared to be complete by 1 month and tended to restore the original surface contour. The synthesis of connective tissue, but not the hyperplasia of the epithelium, was reduced by local steroid treatment. In contrast, an intrastromal keratectomy only stimulated the deposition of small amounts of new connective tissue at the wound junction without as marked a thickening of the overlying epithelium. These observations emphasize the importance of the epithelium in moderating repair after stromal loss, and suggest that remodeling may result in corneal haze and a change in the desired refraction if refractive surgery is attempted by anterior keratectomy.

Endothelial repair in the rat cornea.

Destruction of the central endothelium of the rat cornea was produced by mechanical injury, total debridement, or transcorneal freezing. Endothelial repair was then studied using specular microscopy, histological staining, pachymetry, and autoradiographic analysis of the incorporation of tritiated thymidine into nuclear DNA. Following an initial process of cell slide to cover the endothelial defect, extensive cellular division occurred at the margins of the wound, with approximately 45% of cells in the wound area showing incorporation of tritiated thymidine. An intact monolayer of irregularly shaped cells was reestablished by 2-14 days, depending on the wound. These results suggest that the corneal endothelial repair processes in the rat are more analogous to those of the rabbit than to those of the cat or primate.

Synchrotron x-ray diffraction studies of keratoconus corneal stroma.

The aim of this study was to determine any differences in the collagen molecular and fibrillar packing, or the arrangement of the proteoglycans along the fibril axis, in the stroma of keratoconus and control corneas. High and low-angle x-ray diffraction patterns from the fibrillar and molecular packing of collagen in keratoconus and control corneas were obtained using a synchrotron radiation source. The results indicate no difference in interfibrillar spacing between keratoconus and control corneas at normal physiological hydration, or over a range of hydrations (H = 1-11). This unambiguously demonstrates that the thinning of the stroma that occurs in keratoconus is not a result of closer packing of the collagen fibrils in the stroma. Intermolecular spacings were shown to be significantly (P less than 0.001) lower in keratoconus corneas at normal physiological hydration and over a range of hydrations (H = 1-11). Meridional patterns from the axial distribution of electron density along the collagen fibrils were obtained from untreated control and keratoconus corneas and from the corneas after their proteoglycans were stained with cupromeronic blue. Analysis of the integrated intensities of the first nine orders of these reflections show there is a difference in the staining behavior of collagen-associated proteoglycans in control and keratoconus corneas. Determination of the electron density vectors along the collagen fibrils of cupromeronic blue-stained corneas by the use of Patterson functions indicates that the keratoconus corneal stroma has a specific, ordered proteoglycan that is present in lower numbers along the collagen fibrils, and that it stains less with cupromeronic blue or is in a more disordered arrangement than in the controls.

Delayed dislocation of foldable plate-haptic silicone lenses after Nd:YAG laser anterior capsulotomy.

PURPOSE: To report two eyes (two patients) that had plate haptic silicone intraocular lenses that dislocated 4 weeks after Nd:YAG laser anterior capsulotomy to relieve capsular contraction. METHODS: Case reports. The clinical records of two patients were reviewed. RESULTS: After uncomplicated phacoemulsification with implantation of plate haptic silicone lenses in the capsular bag, two eyes of two patients developed visually notable early contraction of the capsulorhexis. Three radial-relieving incisions approximately 1 mm long were made with a Nd:YAG laser in each eye to enlarge the capsulotomy. Although vision improved, both patients experienced sudden further reduction of vision after approximately 4 weeks. Upon examination of both patients, we noted an extension of an anterior radial capsulotomy incision peripherally, and the intraocular lenses had dislocated from the capsular bag into the ciliary sulcus. CONCLUSIONS: Tears may extend after radial-relieving incisions have been used to enlarge a contracted anterior capsulotomy, possibly because of continued capsular fibrosis. This may allow extrusion of a foldable intraocular lens from the capsular bag.

Conjunctival necrosis after administration of topical fortified aminoglycosides.

We treated 11 episodes of bulbar conjunctival necrosis that occurred in ten patients after therapy for suppurative keratitis with topical fortified aminoglycosides. Chemosis and mucous discharge preceded the development of an area of conjunctival pallor, which stained with fluorescein and was 5 to 10 mm from the corneoscleral limbus. Typical lesions developed in the inferior bulbar conjunctiva after a mean of 4.8 days and 112 mg of gentamicin sulfate (109 drops). The fortified aminoglycoside was the only agent common to all cases. The conjunctival defects healed completely between five and 13 days after treatment was modified to reduce or eliminate aminoglycoside exposure.

In vitro antibiotic resistance in bacterial keratitis in London.

AIM: To document changes in the profile of bacterial isolates from cases of keratitis and changes in their susceptibility to first line antibiotic therapies. METHODS: A retrospective review was performed of all bacterial isolates from cases of keratitis seen between 1984 and 1999. In vitro laboratory susceptibilities to antibiotics were determined by the Kirby-Bauer disc diffusion method. The number of isolates, changes in the proportion of bacterial types, and the number that were fully resistant to monotherapy (ofloxacin), dual therapy (gentamicin and cefuroxime), and prophylactic treatment (chloramphenicol) were calculated. RESULTS: There were 1312 bacterial isolates over 16 years. Gram positive bacteria accounted for 54.7% of isolates and Staphylococcus species (33.4%) were the most frequently isolated organisms. During the study period there has been an increase in the proportion of Pseudomonas species isolates but no overall increase in the proportion of Gram negative isolates. There has not been an increase in the proportion of isolates resistant to ofloxacin since 1995 or an increase in resistance to the combination of gentamicin and cefuroxime. However, since 1984 there has been a significant increase in proportion of Gram negative organisms resistant to chloramphenicol (p=0.0019). CONCLUSIONS: An increase in the in vitro resistance of organisms to first line therapies for bacterial keratitis has not been observed. An increased resistance to chloramphenicol indicates that this drug is unlikely to provide prophylactic cover when Gram negative infection is a risk. Continued monitoring for the emergence of antibiotic resistance is recommended.

Myopia following penetrating keratoplasty for keratoconus.

The frequent occurrence of spherical myopia after penetrating keratoplasty for keratoconus is partly the result of the excessive dioptric power of the grafted cornea which occurs when the diameter selected for the donor button is greater than the diameter of the host incision. This excessive power could be reduced by eliminating disparity between the diameters of the graft and host. To determine what proportion of the myopia in these eyes would persist as a result of axial myopia the axial lengths of 60 patients grafted for keratoconus and 25 emmetropic controls were compared. A keratometry, objective refraction, and contact probe ultrasonic biometry were performed on all eyes. A comparison of the results with a representational schematic eye indicated that the mean spherical refractive error of the grafted keratoconic eyes (-4.83 dioptres) was the combined effect of steepness of the corneal graft (mean radius of curvature 7.46 mm) and an abnormally great axial length (mean 24.84 mm). The increased axial length was mainly the result of elongation of the posterior segment of the globe with a small contribution from an increased anterior chamber depth. Though axial myopia is common in keratoconus, a further study of 70 keratoconic eyes that had not been grafted showed no statistically significant correlation between the posterior segment length and the severity of corneal ectasia. These data suggest that even if excessive corneal power is eliminated after penetrating keratoplasty for keratoconus the associated axial myopia would still produce a mean spherical refractive error of at least -2.8 dioptres.

Effect of age on visual outcome following cataract extraction.

AIM: To determine the effect of age on final corrected visual acuity following cataract extraction. METHODS: A case series of 880 patients aged 60 years and older undergoing cataract extraction between 1996 and 1999 was studied. The best corrected visual acuity was assessed at discharge from the service and the proportion of patients who achieved a postoperative acuity of > or = 6/12 was determined for different age groups. Analysis was also performed after exclusion of patients identified preoperatively as having ocular comorbidity that was thought to limit their final corrected acuity. The odds ratios for visual outcome were calculated for age using multiple logistic regression analysis to adjust for other prognostic factors. RESULTS: A significant age effect was observed, with the proportion of patients who had no ocular comorbidity identified preoperatively and who achieved a visual acuity of > or = 6/12 at discharge decreasing with age (p<0.001). In patients with no comorbidity the odds of achieving an acuity of > or = 6/12 were 4.6 times higher in the 60-69 year age group than in the oldest age group (80+ years). CONCLUSIONS: Age is a significant determinant of visual outcome. This has implications if a points system incorporating an assessment of visual acuity or if visual acuity alone is used to determine the threshold for eligibility for cataract surgery.

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.

Corneal infiltration after recurrent corneal epithelial erosion.

AIMS: To describe the clinical features of patients with a history of recurrent corneal epithelial erosion who develop acute corneal infiltration. METHODS: The records were reviewed of patients who had previously been examined and treated for recurrent corneal epithelial erosion and who presented again with signs suggestive of a microbial keratitis. RESULTS: 11 patients were described; one patient presented with similar signs on two occasions. There was typically a paracentral epithelial defect > 2 mm in diameter with an associated stromal infiltrate and an intense anterior uveitis. Three patients had a hypopyon, and four developed a subepithelial ring infiltrate. Samples were taken for microscopy and bacterial culture, with a positive isolate from two of 12 episodes (16%). Treatment with topical antibiotics and topical corticosteroid resulted in rapid re-epithelialisation and a reduction of inflammation. There was good visual outcome for all eyes, with a recurrence or symptoms of epithelial erosion in only one eye after a mean follow up period of 18 months. CONCLUSIONS: Corneal infiltrates are an uncommon complication of recurrent corneal epithelial erosion. Despite the intensity of the infiltration the majority are culture negative using established techniques. There is typically rapid resolution and a good visual outcome, with a tendency for the episode to mark the end of further symptoms of epithelial erosion.

Quantification of lens opacification with a commercially available lensometer.

A clinical trial was undertaken to determine whether a commercially available lens opacity meter (LM701), which measures backward scattered light from the lens, provides reliable clinical information about the effect of lens opacities on visual acuity. At the 0.001 level of probability we found a significant relationship between the lens opacity meter reading and both the Snellen acuity and patient's age. For a given individual there was also a relationship between the difference in the lens opacity readings between eyes and the difference in the Snellen acuities. We could not demonstrate a relation between the lens opacity reading and either the refractive error, pupil size, or near visual acuity at this level of significance.

Outcome of cataract surgery in patients with retinitis pigmentosa.

AIM: To determine the visual benefit of cataract extraction in patients with retinitis pigmentosa and to identify risk factors for poor outcome. METHODS: A retrospective analysis was undertaken of a continuous series of 142 eyes of 89 patients with retinitis pigmentosa undergoing cataract surgery between 1985 and 1997. RESULTS: Mean age at surgery was 47.5 years (range 24-81 years). In 100 eyes there was posterior subcapsular lens opacity alone, 37 eyes also had moderate nuclear sclerosis, and five had only nuclear sclerosis. All patients had central visual fields of <10 degrees. Overall, mean visual acuity improved from 1.05 (SD 0.38) preoperatively to 0.63 (SD 0.49) postoperatively on the logMAR scale. Significant postoperative capsular opacification occurred in 88/139 eyes (63%) and 45.1% required capsulotomy. Anterior capsulotomy was undertaken in 5/52 (9.6%) eyes undergoing phacoemulsification. Postoperative macular oedema was noted in 20 (14%) eyes. Visual acuity improved in 109 eyes (77%), was unchanged in 29 eyes (20.5%), and worsened after surgery in four eyes (2.5%). 86/89 patients reported major improvement of visual function. CONCLUSIONS: Cataract surgery for relatively minor lens opacities is beneficial in patients with retinitis pigmentosa, and most report subjective improvement of visual symptoms. The incidence of capsular opacification is high and anterior capsular contraction may occur. The number of eyes with poor vision due to macular oedema was unexpectedly low.

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.

Early decentration of plate-haptic silicone intraocular lenses.

We report 4 eyes of a consecutive series of 1299 that developed early decentration of a 10.5 mm diameter plate-haptic silicone intraocular lens (IOL) after uneventful phacoemulsification. All eyes had an intact continuous curvilinear capsulorhexis (CCC) with the IOL placed in the capsular bag. After an initial period of good vision, patients noted the onset of glare or monocular diplopia between 1 and 5 weeks after surgery. On examination, there was no significant anterior capsule contraction; however, the edge of the IOL optic was visible in the undilated pupil. There was adhesion between the anterior and posterior capsules at the margin of the CCC that maintained the IOL decentration. Decentration recurred in 1 eye after the IOL was rotated 90 degrees and recentered. Symptoms resolved in 3 eyes after the IOL was removed and replaced with a rigid IOL with a larger diameter optic.

Long-term refraction and keratometry after penetrating keratoplasty for keratoconus.

We looked for continued corneal ectasia after penetrating keratoplasty (PK) for keratoconus by measuring long-term changes in keratometry and refraction after final suture removal. The records of 587 patients who had had PK for keratoconus and who had attended a single center over a 7-year period were examined. For 184 eyes keratometry or refraction data were available from the first operated eye from the 6-month interval after final suture removal, and, in these patients, these readings were repeated as they continued to be seen for review. The changes in mean keratometry, spherical equivalent, and cylinder over the period of follow-up were then calculated, and these data were assessed by regression analysis. We found no significant change with time in the amount of cylinder when measured by either refraction or keratometry. There was a trend (p = 0.075) toward an increase in the mean keratometry with time, suggesting a gradual flattening of the cornea, and there was a clinically small, but statistically significant (p < 0.001), time-dependent increase in the residual myopia in the years after final suture removal. In conclusion, we found a wide range in the individual values for changes in keratometry or refraction in the years after suture removal following PK for keratoconus but no evidence overall to suggest continued corneal ectasia or a recurrence of keratoconus in these grafts.

Iris ischaemia following penetrating keratoplasty for keratoconus (Urrets-Zavalia syndrome)

A fixed and dilated pupil is an uncommon postoperative complication after penetrating keratoplasty (PK) for keratoconus. Although the clinical features have been well described, the precise aetiology is uncertain. We performed anterior segment fluorescein angiography in the early postoperative period on three patients who developed fixed, dilated pupils after apparently uncomplicated surgery. All of the eyes had severe iris ischaemia. A possible role for a postoperative rise in intraocular pressure in the aetiology of this syndrome is discussed.

A histochemical and x-ray diffraction study of keratoconus epikeratoplasty. Report of two cases.

Two epikeratoplasty lenticules (Epi-L) with keratoconus host corneas (Epi-H) were removed by penetrating keratoplasty because of poor visual acuity although they were clinically clear. Light microscopy showed that the keratocytes were underpopulated and unevenly distributed in Epi-L. Transmission electron microscopy showed that abnormal sized proteoglycans (PGs) were unevenly accumulated in the stromas of both Epi-L and Epi-H. The low-angle x-ray diffraction results from case 1 showed lower collagen interfibrillar spacings, compared with those from one keratoconus cornea, seven cryolenticules, and four normal human corneas. The fibril diameters and the collagen axial periodicity D were similar in all tissues. Allowing selected samples to swell, the interfibrillar spacing increased by 30.6-45.5% in Epi-H and by 29.8% in the keratoconus control. However, it increased by only 7.6-9.7% in Epi-L and by 11.4% in a cryolenticule. The uneven distribution of PGs and the lower interfibrillar spacings in the swollen lenticules suggest that there is an uneven distribution of water in different parts of the Epi-L and Epi-H stromas. This may lead to a variation of the refractive index or optical properties in the stroma and the deterioration of the visual image, which may explain the poor visual results.

Assessment of the effect of oral clarithromycin on visual outcome following presumed bacterial endophthalmitis.

PURPOSE: The use of clarithromycin was assessed as a biofilm reducing agent in the management of bacterial endophthalmitis. METHODS: 84 eyes of 83 patients presenting with clinical signs highly suggestive of bacterial endophthalmitis were treated using a standard regimen of intraocular vancomycin, amikacin and systemic steroids, which in addition included oral clarithromycin. Ocular penetration of oral clarithromycin in healthy and inflamed eyes was also assessed. RESULTS: Comparing visual acuities at presentation and 6 months, 66% of patients demonstrated an improvement. Intraocular samples were culture positive in 58% of eyes. As compared to culture positive cases, more culture negative cases achieved a visual acuity of 6/12 or better (p = 0.0047). As compared to patients receiving the standard protocol but without clarithromycin, a greater number of culture negative cases demonstrated an improvement in vision of > or = + 6 Snellen lines (p = 0.023). The ocular penetration of clarithromycin into the anterior chamber of inflamed eyes appears sufficient to allow anti-biofilm activity against bacteria at the basic pH encountered in eyes with endophthalmitis. CONCLUSIONS: The ocular penetration of clarithromycin appears adequate for anti-biofilm activity in inflamed eyes. The beneficial effects of oral clarithromycin on visual outcome has been demonstrated in culture negative eyes with clinical signs highly suggestive of bacterial endophthalmitis. The final visual outcome for culture positive cases remains poor.

Corneal toxic changes after cataract extraction.

Over an 18-month period 10 patients (12 eyes) presented with severe corneal toxic changes after cataract extraction. Defined stages in the keratopathy included punctate epithelial keratopathy, pseudodendrite, central epithelial ulcer and central stromal ulcer. Periods of up to 13 months were required for resolution of the defects. Axial scarring and nonhealing epithelial defects resulted in a final visual acuity of counting fingers and hand movement in two patients. We believe that exposure during the postoperative period to benzalkonium chloride contained in ophthalmic medications represents the most likely cause of the toxic changes and that no single ophthalmic medication can be held responsible. The past ocular histories of the patients included chronic open-angle glaucoma, dry eye syndrome and anterior membrane dystrophy. Prior exposure to benzalkonium-containing antiglaucoma medications, tear film deficiencies or abnormalities of epithelial adhesion may have predisposed the corneas in these patients to the development of benzalkonium-related toxic changes.

Toxocariasis: a neglected entity.

Toxocara canis infects many dogs yet has been seldom implicated as a cause of human disease in New Zealand. Nine patients with diagnostic titres for Toxocara canis who were seen in Christchurch Hospital over a five-year period are described. Ophthalmoscopic signs of toxocaral infection were visible at the optic disc or posterior pole of all ten affected eyes. A localised disciform detachment of the macula or a focal granuloma on the disc or retina were the commonest lesions. Vision was reduced to 6/60 or less in five affected eyes while the remaining five eyes lost 2-4 lines of vision on the test chart.