Subthreshold diode micropulse photocoagulation for the treatment of clinically significant diabetic macular oedema.

AIM: To report the visual and clinical outcomes of a pilot study of subthreshold diode micropulse (SDM) laser photocoagulation for clinically significant diabetic macular oedema (CSMO). METHODS: The results of infrared (810 nm) SDM laser photocoagulation for CSMO were retrospectively reviewed in 95 eyes of 69 consecutive patients with mild to moderate non-proliferative diabetic retinopathy. The same laser parameters were used for each patient. Only the number of laser applications varied between patients, depending on their macular findings. Primary outcome measures were Snellen visual acuity, fluorescein angiographic leakage, and CSMO status. RESULTS: Visual acuity was stable or improved in 85% of treated eyes, with a mean follow up of 12.2 months (range 3-29 months). CSMO decreased in 96% and resolved in 79% of treated eyes. No adverse laser events occurred. No laser lesions were detectable ophthalmoscopically or angiographically after treatment, consistent with calculations based on ANSI Z136.1 laser safety standards suggestive of only histologically detectable tissue effects at the laser exposure levels. No laser scarring was observed during the follow up period. CONCLUSION: Subthreshold diode micropulse laser photocoagulation minimises chorioretinal damage in the management of CSMO and demonstrates a beneficial effect on visual acuity and CSMO resolution. Prospective studies are needed to fully evaluate this technique.

Nd:YAG capsulotomy rates after use of the AcrySof acrylic three piece and one piece intraocular lenses.

BACKGROUND/AIM: Acrylic lens size and shape may influence the rate of posterior capsule opacification (PCO) and need for Nd:YAG capsulotomy. The aim of this study is to compare the Nd:YAG capsulotomy rate of the three piece acrylic/PMMA AcrySof MA series lens with the one piece acrylic AcrySof SA series lens. METHODS: 434 eyes of 329 patients who had cataract extraction and implantation of one of four types of intraocular lenses (IOLs) were evaluated for rate of Nd:YAG capsulotomy. 176 eyes received the acrylic AcrySof MA30AC IOL, 71 eyes the acrylic AcrySof MA60AC IOL, 45 eyes the acrylic AcrySof SA30AL IOL, and 142 eyes the acrylic AcrySof SA60AT IOL. RESULTS: The rates of Nd:YAG capsulotomy with the three piece IOL (MA30AC/MA60AC) and the one piece IOL (SA30AL/SA60AT) were 1.2% and 2.1% at 6 months, 2.8% and 5.9% at 12 months, and 3.6% and 7.5% at 24 months, respectively. The incidence of Nd:YAG capsulotomy was higher in patients who received the one piece IOL (p=0.01, log rank test). There was no difference in Nd:YAG capsulotomy rates when comparing lens optic size, age, sex, history of pars plana vitrectomy, and diabetes mellitus. CONCLUSIONS: This study shows a greater incidence of Nd:YAG capsulotomy in patients who receive one piece acrylic AcrySof lenses when compared to those who receive three piece acrylic AcrySof lenses.

Brain biopsy in primary angiitis of the central nervous system.

To determine the yield of brain biopsy and the predictive value of clinical features and ancillary studies, we retrospectively analyzed hospital chart data from 61 consecutive patients suspected of having primary angiitis of the CNS (PACNS). Biopsies disclosed PACNS in 22 (36%), alternative diagnoses in 24 (39%), and no diagnosis in 15 (25%). Clinical indicators and angiography were not useful predictors of PACNS. Brain biopsy should be the primary diagnostic tool in this setting because of the poor reliability of other indicators and because of the high yield of alternative diagnoses requiring different management.

Effect of 1% sodium hyaluronate (Healon) on a nonregenerating (feline) corneal endothelium.

A series of experiments were performed to investigate the effect of 1% sodium hyaluronate (Healon) on the nonregenerating corneal endothelium of the cat. Aqueous humor replacement with 1% sodium hyaluronate resulted in mild, transient elevations of intraocular pressure compared to eyes that were injected with balanced salt solution. Sodium hyaluronate 1% protected the feline endothelium against cell loss incurred by contact with hyaluronate-coated intraocular lenses compared to endothelial contact with lenses that were not coated with sodium hyaluronate. The use of intraoperative 1% sodium hyaluronate, however, did not protect against endothelial cell loss incurred by penetrating keratoplasty or prevent subsequent skin graft-induced corneal homograft rejections. Homograft rejections were milder, however, in some eyes that received grafts coated with 1% sodium hyaluronate. Image analysis of photographs of trypan blue- and alizarin red-stained corneal buttons after trephining, stretching of Descemet's membrane, rubbing against iris-lens preparations, or immediately after penetrating keratoplasty demonstrated that the stretching of the posterior cornea is an important cause of endothelial damage that would not be protected against by a viscoelastic coating.

Glutathione peroxidase-1 deficiency leads to increased nuclear light scattering, membrane damage, and cataract formation in gene-knockout mice.

PURPOSE: Previous in vitro studies with transgenic and gene-knockout mice have shown that lenses with elevated levels of glutathione peroxidase (GPX)-1 activity are able to resist the cytotoxic effect of H(2)O(2), compared with normal lenses and lenses from GPX-1-deficient animals. The purpose of this study was to investigate the functional role of this enzyme in antioxidant mechanisms of lens in vivo by comparing lens changes of gene-knockout mice with age-matched control animals. METHODS: In vivo lens changes were monitored by slit lamp biomicroscopy, and enucleated lenses were examined under a stereomicroscope in gene-knockout animals and age-matched control animals ranging in age from 3 weeks to 18 months. Transmission (TEM) and confocal microscopy were performed on different regions of lenses after the mice were killed at various times. RESULTS: Slit lamp images showed an increase in nuclear light scattering (NLS) in gene-knockout mice compared with control animals. TEM revealed changes in the nucleus as early as 3 weeks of age by the appearance of waviness of fiber membranes. With increasing age, there was greater distortion of fiber membranes and distension of interfiber space at the apex of fiber cells compared with control mice. The changes in nuclear fiber membranes were even more dramatic, as observed by confocal microscopy, which was performed on thicker sections. In contrast to the changes in the lens nucleus, the morphology of the epithelium and superficial cortex remained unchanged in knockout animals during the same experimental period, consistent with slit lamp observations. Stereomicroscopy of ex vivo lenses demonstrated a significant increase in opacification in gene-knockout mice relative to control animals of the same age. This effect became evident in mice aged 5 to 9.9 months and persisted thereafter in older animals, resulting in mature cataracts after 15 months. CONCLUSIONS: The results demonstrate the critical role of GPX-1 in antioxidant defense mechanisms of the lens nucleus. The increased NLS appears to be associated with damage to fiber membranes in the nucleus, which is particularly susceptible to oxidative challenge because of the deficiency of GPX-1. It is suggested that the lens membrane changes in the knockout animals may be due to the formation of lipid peroxides, which serve as substrates for GPX-1. Cataract development in gene-knockout mice appeared to progress from focal opacities, apparent at an earlier age, to lamellar cataracts between 6 and 10 months, and finally to complete opacification in animals older than 15 months. This is the first reported phenotype in GPX-1-knockout mice.

Enhanced healing of cat corneal endothelial wounds by epidermal growth factor.

PURPOSE: The authors investigated whether healing of cat corneal endothelial wounds could be enhanced in vivo by human epidermal growth factor (EGF). METHODS: EGF was administered in sodium hyaluronate to the anterior chamber of cats after an endothelial touch injury. Control contralateral eyes received sodium hyaluronate alone. At selected times after injury, the corneas were evaluated for thickness, the rate of endothelial wound closure, the endothelial cell density, any variation in cell size, the percentage of hexagonal cells, and endothelial cell mitosis. RESULTS: Two days after injury, endothelial wounds of eyes treated with EGF had healed an average of 65 +/- 4% of the initial 38.5 mm2 wound area; paired control eyes had healed an average of 59 +/- 4% (P < 0.05). Both EGF-treated and control wounds had resurfaced over 90% of the initial wound area on day 4 after injury, and the wounds were completely resurfaced by 7 and 14 days after injury in both treatment groups. On days 4 and 7 after injury, the EGF-treated corneas were 5% and 8% thicker (835 versus 796 microns and 786 versus 728 microns, respectively) than the paired control corneas (P < 0.03). On days 10 and 14 after injury, both EGF-treated and control corneas were 19% and 12% thicker, respectively, than prewound the corneal thickness (621 microns). Seven days after injury, the corneas treated with EGF had an average of 76 +/- 28% more (P < 0.05) endothelial cell nuclei labeled with tritiated thymidine compared with that of the paired control eyes (2472 versus 1543 labeled nuclei). Fourteen days after injury, the central endothelial cell density of EGF-treated corneas was an average of 38 +/- 11% higher than that of the paired control eyes (P < 0.01, 1708 versus 1235 cells/mm2). The percentage of hexagonal cells in the wound area was an average of 14 +/- 4% higher (P < 0.01) than that of the paired control eyes (82% versus 69%), and the coefficient of variation of the cell size for EGF-treated corneas was an average of 31% (P < 0.05) smaller than that of the paired control corneas (0.21 versus 0.29 [standard deviation]/mean cell size). CONCLUSIONS: A single intraocular application of EGF formulated in sodium hyaluronate after an endothelial cell injury significantly enhanced multiple parameters that are closely related to improved endothelial cell regeneration.

The effect of removing running sutures on astigmatism after penetrating keratoplasty.

To evaluate astigmatic change after removal of the double running sutures used in penetrating keratoplasty, all patients (N = 131) in the Michigan Corneal Transplantation Patient Registry, Ann Arbor, whose eyes were phakic after penetrating keratoplasty were evaluated. The primary reasons for surgery in this group were keratoconus (n = 44, 34%) and Fuchs' corneal dystrophy (n = 19, 15%). The average effect of 10-0 suture removal in 58 eyes with documented keratometry readings was a 0.30-diopter (D) decrease in astigmatism, with 59% showing 2 D or less of astigmatic change. In 83 eyes with keratometry readings before and after 11-0 suture removal, an average increase of 0.37 D of astigmatism was observed, with 81% showing less than 2 D of astigmatic change. In eyes that were highly astigmatic (greater than 6 D) before suture removal, a reduction in astigmatism exceeding 2 D was observed in 39% and 11% after 10-0 and 11-0 suture removal, respectively.

Predictive factors for endothelial cell loss after penetrating keratoplasty.

To assess the influence of donor age, donor endothelial cell density, recipient age, and diagnosis on loss of endothelial cell density after penetrating keratoplasty, we evaluated endothelial cell density data from specular endothelial images collected during the follow-up penetrating keratoplasty surgeries performed from 1980 through 1985 at one center. Univariate and multivariate analyses of information from 265 grafts showed consistent and statistically significant associations between 1-year postoperative loss of endothelial cell density and donor age, donor endothelial cell density, and recipient age. Corneas obtained from older donors, corneas with higher donor endothelial cell density, and corneas transplanted to older recipients demonstrated greater percentage of loss of endothelial cell density 1 year after surgery. These three factors accounted for 17% of the total variance in percentage of loss of endothelial cell density 1 year after surgery.

Demographic and predisposing factors in corneal ulceration.

We identified 224 patients hospitalized with corneal ulcerations at the University of Michigan Hospitals, Ann Arbor, between May 1975 and September 1981, and performed a chart review on a random sample of these cases. Bimodality in the patients' age distribution was attributed to nonsurgical ocular trauma in the younger group, and predisposing keratitis, surgical trauma, bullous keratopathy, and entropion in the older group. Bacterial and postherpetic causes accounted for 52 (52%) of the sampled cases. Pseudomonas aeruginosa and Staphylococcus aureus were the major isolates. Important predisposing factors included nonsurgical and surgical trauma, herpetic keratitis, contact lens wear, corticosteroid therapy, and bullous keratopathy. Both age and visual acuity on admission had prognostic implications for improvement in visual acuity after treatment.

Significance of cilioretinal arteries in primary open angle glaucoma.

Greater optic nerve and visual field damage has been reported in eyes with primary open angle glaucoma that also have cilioretinal arteries compared with fellow eyes that do not have cilioretinal arteries. The cilioretinal artery may shunt blood from the posterior ciliary arterial circulation away from the optic nerve, especially in the inferior and superior optic disc, where early glaucomatous damage often occurs. To evaluate these observations, we reviewed stereoscopic disc photographs of 122 patients with primary open angle glaucoma. Twenty-one patients had unilateral cilioretinal arteries and bilateral primary open angle glaucoma with an intraocular pressure greater than 21 mm Hg at presentation and a difference of 3 mm Hg or less between the eyes. Stereoscopic disc photographs and Goldmann visual fields were evaluated in a masked fashion. In glaucomatous eyes with comparable intraocular pressures, we found no significant optic nerve or visual field differences in eyes with cilioretinal arteries compared with eyes without cilioretinal arteries.

Positional effects on exophthalmometer readings in Graves' eye disease.

Forty-eight patients with Graves' eye disease, half of whom had extraocular muscle restriction, and 45 normal adult subjects underwent exophthalmometry while in the upright and the supine positions to determine whether the difference in measurement due to position would serve to differentiate the groups. A previous report claimed that the upright reading would be greater than the supine reading for normal subjects and patients with Graves' eye disease without clinical extraocular muscle involvement, whereas those with extraocular muscle restriction would show little change in their exophthalmometer readings. Our study showed an increase in exophthalmometer readings in going from the upright to the supine position for normal subjects and both groups of patients with Graves' eye disease. Furthermore, this test did not serve to differentiate these three groups.

Oversized donor grafts in penetrating keratoplasty. A randomized trial.

One hundred seventy-three aphakic or phakic corneal transplants were analyzed in a prospective randomized study to determine the effect of oversized corneal donor buttons on intraocular pressure, corneal curvature and astigmatism, wound dehiscence, and anterior chamber depth. We compared 93 oversized grafts with 80 same-sized grafts. In aphakic eyes, oversized grafts showed a trend toward lower incidence of elevated intraocular pressure during the early post-operative period and lower prevalence of glaucoma at the final visit, although this was not statistically significant. No such trends were seen in phakic eyes. Postoperative corneal curvature was significantly steeper in oversized than same-sized grafts, in both phakic and aphakic eyes; there was no difference in postoperative astigmatism. Anterior chamber depth was significantly greater in oversized grafts. Of four wound dehiscences, all occurred in same-sized grafts.

Retinal detachment following penetrating keratoplasty.

The time-related risk of retinal detachment during the follow-up of 1146 penetrating keratoplasty procedures was evaluated, using survival analysis techniques. Twenty-eight retinal detachments were observed during follow-up. The Kaplan-Meier estimate of the risk of developing retinal detachment increased from 1.5% at three months to 2.1% at one year after surgery. Further follow-up showed a gradual increase in the cumulative proportion developing retinal detachment to 4.7% at 3.5 years after surgery. Of the preoperative and intraoperative factors available for study, performing an anterior vitrectomy during penetrating keratoplasty was associated with a greater risk of postoperative retinal detachment. The outcome of visual acuity following retinal detachment in these patients' eyes was poor; five patients could not perceive light with the affected eye, and 82% (23/28) had visual acuity of 20/200 or less.

Antiviral therapy after penetrating keratoplasty for herpes simplex keratitis.

OBJECTIVE: To assess the efficacy of prophylactic topical antiviral therapy after penetrating keratoplasty for herpes simplex keratitis in the postoperative period and during the treatment of allograft rejection episodes with topical steroids. We used these data to make predictions of the sample size required to perform a prospective study of prophylactic oral acyclovir in the postoperative period. DESIGN: Retrospective review. SETTING: A university referral cornea service. PATIENTS: One hundred thirty-two consecutive penetrating keratoplasties for herpes simplex keratitis in 119 eyes of 118 patients. Only four grafts were performed in actively inflamed eyes. INTERVENTIONS: Sixty-six (52%) of the grafts performed in quiescent eyes received prophylactic postoperative topical antiviral treatment, three (2%) received oral acyclovir, and 59 (46%) received no antiviral therapy. The mean (+/- SD) duration of antiviral therapy was 12.8 +/- 22.5 months. MAIN OUTCOME MEASURES: Herpetic recurrence, allograft rejection episodes, and graft failure. RESULTS: Multivariate analysis showed that early antiviral use was associated with a decreased risk of herpes simplex keratitis recurrence (relative risk [RR] = 0.44; 95% confidence interval [CI], 0.21 to 0.94; P = .007) and allograft rejection (RR = 0.43; 95% CI, 0.25 to 0.75; P = .002). Graft failure was associated with herpetic recurrence within the first year (RR = 2.25; 95% CI, 1.09 to 4.64; P = .001) and allograft rejection episodes (RR = 2.56; 95% CI, 1.20 to 5.26; P = .003). Using these data, a prospective trial of postoperative oral acyclovir would require between 59 and 112 patients per group. CONCLUSIONS: Postoperative prophylactic antiviral treatment is associated with decreased rates of herpes simplex viral keratitis recurrence and allograft rejection. Early recurrence is associated with an increased risk of graft failure. A prospective study of postoperative oral acyclovir would require a multicentered approach.

Implantation of posterior chamber intraocular lenses in the absence of lens capsule during penetrating keratoplasty.

We retrospectively studied the clinical records and the corneal endothelial cell counts of 133 consecutive eyes that received sutured posterior chamber intraocular lenses during penetrating keratoplasty in the absence of lens capsular support. Postoperative follow-up time ranged from three to 24 months, with 82 patients having at least one year of follow-up. At one year, 45.1% of these patients had 20/40 or better visual acuity, 30.5% had a visual acuity between 20/50 and 20/100, and 24.4% had a visual acuity of 20/200 or worse. At two years, 63.6% had a visual acuity of 20/40 or better, 18.2% had a visual acuity between 20/50 and 20/100, and 18.2% had a visual acuity of 20/200 or worse. Ninety-seven percent of the grafts remained clear at their latest follow-up examination. Cystoid macular edema (36.4%) and age-related macular degeneration (14.0%) accounted for poor visual acuity in most cases. Less common problems included graft rejection, retinal detachment, glaucoma, and endophthalmitis. At one year, the endothelial cell loss in the grafts averaged 19% with sutured posterior chamber intraocular lenses.

Treatment of blepharospasm with botulinum toxin. A preliminary report.

The effects of botulinum A toxin injections for the treatment of facial spasm were analyzed for 22 patients. Sixteen patients had unoperated on essential blepharospasm, three had essential blepharospasm with residual spasm following previous surgical treatment, and three had unoperated on hemifacial spasm. Treatment was effective for most patients, but transient, with the mean interval of relief of spasm after the first injections being ten weeks. The injection of botulinum toxin reduced the maximum lid force by about 10%. While side effects were common, they were generally mild and well tolerated. No cumulative effect of botulinum toxin was evident in those receiving three series of injections. There is no significant difference in either the interval free of spasm or the rate of lid-force recovery following any of three sequential injections of increasing doses of botulinum toxin.

Time course of thymoxamine reversal of phenylephrine-induced mydriasis.

We conducted a randomized, double-masked, paired comparison of 0.1% thymoxamine vs placebo for the reversal of phenylephrine-induced mydriasis. Mydriasis was induced with 2.5% phenylephrine in each eye of 74 subjects (148 eyes). Each subject then received 0.1% thymoxamine in one eye and placebo in the other eye. Pupillary measurements were obtained at regular intervals during the ensuing 8 hours. At all intervals, a greater percentage of thymoxamine-treated eyes returned to baseline pupillary diameters compared with placebo-treated eyes (P less than or equal to .01). For subjects in whom both pupils returned to baseline, thymoxamine-treated eyes returned to baseline in a mean of 2.2 hours, vs 5.2 hours for placebo (P less than .0001). Among thymoxamine-treated eyes, those with light irides responded more rapidly than those with dark irides, returning to baseline in 1.6 vs 2.8 hours, respectively (P = .0046). After constriction to baseline pupillary diameter had been achieved, no patients experienced a rebound dilation.

A randomized, prospective, double-masked clinical trial of Optisol vs DexSol corneal storage media.

We compared Optisol and DexSol, two chondroitin-sulfate-based media for corneal storage at 4 degrees C, by transplanting 31 donor cornea pairs (one cornea stored in Optisol and its mate in DexSol for 20 to 134 hours) into 31 pairs of recipients (62 patients). All grafts were clear 1 year after transplantation except for one primary donor failure (Optisol group). Optisol-stored corneas were significantly thinner than DexSol-stored corneas after cardinal suture placement (0.64 mm vs 0.76 mm) and at the end of surgery (0.69 mm vs 0.78 mm); at all points afterward through 1 year the two groups did not differ. The activity of two lysosomal enzymes released into the media during storage, alpha-mannosidase and alpha-glucosidase, was lower in the Optisol group. Epithelial status and all endothelial morphometric parameters, except the figure coefficient at 1 year, did not differ between the two groups before surgery and 3, 6, and 12 months after surgery. Mean endothelial cell loss at 1 year was 15% for the Optisol group and 21% for the DexSol group (P = .22). Thus, Optisol-stored corneas were thinner during surgery than DexSol-stored corneas and there was less lysosomal enzyme activity in the Optisol medium after tissue storage. There were no significant differences in postoperative clinical or endothelial morphometric parameters, however.

Assessment of success and complications of triple procedure surgery.

In an effort to quantify both the success and complications of triple procedure surgery, we studied a consecutive series of 166 patients who underwent this procedure. The average length of follow-up was 17 months. Of 166 patients, 138 (83%) achieved a visual acuity of 20/40 or better after surgery; in the most recent 52 patients, 26 (50%) achieved this within two months. The most frequent complications during the postoperative period were glaucoma (40 patients, 24%), endothelial graft rejection episodes (two-year cumulative risk, 16%), and astigmatism (mean keratometric cylinder, 4.97 D). Additional surgical interventions were required in 27 patients (16%).

Topical fibronectin ophthalmic solution in the treatment of persistent defects of the corneal epithelium. Chiron Vision Fibronectin Study Group.

PURPOSE: We sought to evaluate the efficacy of topical fibronectin ophthalmic solution, containing 3.5 mg/ml of human fibronectin, in the treatment of persistent epithelial defects of the cornea. METHODS: In a double-masked, randomized clinical trial, patients with a persistent, corneal epithelial defect of at least 14 days in duration, and at least 2 mm in width along the larger axis, were sought from the practices of 38 clinical investigators. After a 14-day washout period, 65 patients were randomly assigned to one of three treatment groups. One group (n = 20) received fibronectin drops; the second (n = 23) received drops of the vehicle from the fibronectin solution; and the third (n = 22) received a placebo. RESULTS: After 21 days of treatment, there was no difference in percentage reduction of the corneal epithelial defect size; the average percentage of reduction of defect area ranged from 46.5% to 54.3%. Fibronectin treatment showed a beneficial effect for patients with larger baseline defects (10 mm2 or greater in area); however, no such effect was observed among patients with smaller defects. Defect duration before treatment had a significant effect on outcome (P = .007); defects of longer duration were less likely to decrease in size over the course of the study. CONCLUSIONS: All three treatment groups showed similar reductions in defect size; therefore, this study provides no support for the efficacy of fibronectin treatment of persistent, corneal epithelial defects. Defect duration showed a negative association with reduction in defect size. Because strict control of topical applications during the washout and treatment periods resulted in beneficial responses, physicians should carefully consider the topical medications used by patients who have persistent, corneal epithelial defects.