Effect of phenylephrine on normal and regenerated endothelial cells in cat cornea.

Topical commercial phenylephrine HCl (Neo-Synephrine 10%) has been shown to cause an increase in corneal thickness and reversible vacuolization of corneal endothelial cells in rabbits. Using an in vivo model of regenerated corneal endothelial cells in the cat, we compared the cytotoxicity of phenylephrine-HCl 10% to regenerated and to normal, nonregenerated cells. Following removal of the epithelium, topical application of the drug causes the appearance of anterior and posterior bands of stromal edema and reversible vacuolization in both normal and regenerated endothelial cells. Phenylephrine was not more damaging to the regenerated cells. Polymorphonuclear leukocytes infiltrated between the regenerating cells 24 hr after treatment but did not appear to destroy them. Phenylephrine may therefore be implicated as a causative factor of corneal edema and postoperative inflammation.

Neurotrophic corneal ulcers in diabetes mellitus.

Three patients with juvenile-onset insulin-dependent diabetes mellitus had neurotrophic keratitis and/or ulceration presumably related to their diabetes. We suggest that significant neurotrophic corneal disease can occur in diabetic patients. The neurotrophic keratitis and corneal ulcers responded to treatment.

Response of the corneal endothelium to cataract surgery.

Regional changes in endothelial cell density, morphology, and corneal thickness were serially examined with a specular microscope after intracapsular cataract extraction (four eyes), extracapsular cataract extraction (five eyes), and extracapsular cataract extraction with posterior chamber lens implantation (13 eyes). Regardless of the type of cataract surgery, cell loss and morphologic changes (decreased percentage of hexagonal cells, increased cellular elongation, and increased coefficient of variation) were greatest and occurred within one week in the superior cornea. Similar changes occurred after one month centrally but were minimal inferiorly. Endothelial cell density stabilized, and the morphologic changes resolved within three months in all regions of the cornea. Corneal swelling resolved within one month. Differences between the procedures were noted only in the superior portion of endothelium, where cell loss and morphologic changes were greatest following intracapsular cataract extraction. Also, endothelial wound healing was complete and stable three months after cataract surgery, with or without posterior chamber lens implantation.

Effects of timolol on bovine corneal endothelial cultures.

The chronic use of timolol (Timoptic) maleate to control glaucoma may produce cytotoxic complications in the cornea. We have therefore compared the relative toxic effects of the commercial ophthalmic preparation with that of the pure compound. Commercial vehicle, either with or without 16 mM timolol maleate, killed cultures within the first five minutes of exposure. Pure timolol maleate, however, caused rapid but reversible cellular contractions, and cells remained viable in it for over 24 hours. Dilution with culture medium reduced both the cytotoxicity and the speed of the contractions. Incubation in 1:100 dilutions of vehicle or commercial drug preparations or in 0.16 mM pure timolol maleate did not alter cellular morphology. The results indicate that while undiluted vehicle is toxic, timolol maleate is not.

Trifluridine in resistant human herpetic keratitis.

Patients with active dendritic herpetic keratitis that was unresponsive to topical idoxuridine or vidarabine therapy were treated topically with a 1% solution of trifluridine. The dendritic ulcers healed in an average time of 6.1 days. All patients tolerated the drug well except for one patient in whom a reversible crystalline epithelial keratitis developed.

The effect of phenylephrine on the cornea.

Rabbit corneas were treated with three drops of phenylephrine hydrochloride with the epithelium intact or denuded. Corneal thickness was measured before and after drug treatment, and at various times after treatment the corneas were fixed for scanning and transmission electron microscopic observation. The results of this study show that phenylephrine caused a dramatic increase in corneal thickness (drug-induced edema) and cellular vacuolation within the keratocytes and endothelial cells in the corneas without the epithelium. Corneal thickness did not change and the ultrastructural changes were minimal following drug application in those corneas with the epithelium intact. Results of this study also suggest that phenylephrine has a cytotoxic effect on the corneal endothelium and keratocytes when used in corneas where the epithelium has been removed. In coreas with intact epithelium, the damage was less severe and limited to the epithelium.

Intraocular irrigating solutions. Their effect on the corneal endothelium.

The effects of several intraocular irrigating solutions on the corneal endothelium of rabbit and monkey corneas were evaluated, utilizing a specular microscope perfusion system with both scanning and transmission electron microscopy. Corneas perfused with 0.9% sterile isotonic physiological saline swell at a rate of 60mum to 90mum/hr; endothelial cells separate from each other and show extensive degenerative changes. Corneas perfused with lactated Ringer solution swell at a rate of 37mum to 40mum/hr, and the endothelial cells show slower, but progressive degeneration. Corneas perfused with balanced salt solution swell at 24mum to 31mum/hr, and degenerative changes become severe only after two hours. Corneas perfused with Ringer solution containing bicarbonate, reduced glutathione, and adenosine do not increase in thickness, and there is minimal deterioration of endothelial ultrastructure for periods of up to six hours.

Accuracy of scanning laser polarimetry in the diagnosis of glaucoma.

OBJECTIVE: To determine the diagnostic accuracy of scanning laser polarimetry. SUBJECTS AND METHODS: A total of 95 healthy subjects and 102 patients with glaucoma met all inclusion criteria. Data collected on each participant included an automated visual field examination, stereoview optic nerve head photographs, intraocular pressure measurement, and a screening and full scanning laser polarimetry study. Each participant was classified as "normal," "glaucoma," or "uncertain" by each of 3 ophthalmologists based on all available clinical information, with the exception of the scanning laser polarimetry results. Before data analysis, 4 diagnostic algorithms for the full-test mode and 2 for the screening mode were chosen to be evaluated for their sensitivity and specificity in detecting glaucoma. RESULTS: Of the 4 algorithms tested for the full-test mode, "the number" (abnormal test score, >35) had sensitivities of 57%, 71%, and 81% for early, moderate, and severe glaucoma, respectively. Specificity was 89%. For the screening test, sensitivities were much lower, particularly for those with severe glaucoma damage. CONCLUSIONS AND CLINICAL RELEVANCE: Scanning laser polarimetry can help to differentiate subjects with normal findings from patients with glaucomatous damage. Even the best algorithm tested, however, failed to detect a substantial number of subjects with severe damage. Further study is needed before scanning laser polarimetry can be recommended as a screening method for glaucoma.

Corneal preservation: recent advances.

New methods of corneal preservation for penetrating keratoplasty have recently been developed to meet the increasing demand for donor corneal tissue. Techniques utilized in the laboratory to evaluate the viability of the corneal endothelium and the clinical results obtained with each method are discussed. All of the new methods (storage in serum or McCarey-Kaufman medium, cryopreservation and organ culture) required excision of the cornea from the donor eye. Good clinical results have been obtained in several ophthalmology centers with cryopreservation and storage in McCarey-Kaufman (M-K) medium. Storage in M-K medium has rapidly become popular because it is a simple and inexpensive method and appears to maintain endothelial viability for about 4 days. Cryopreservation is a more complicated procedure, but it enables longterm storage of donor tissue. Organ culture is still experimental and requires careful technique, but offers promise of maintaining endothelial viability for 3 to 4 weeks.

Penetrating keratoplasty for pseudophakic bullous keratopathy after extracapsular cataract extraction.

Seventeen women underwent simple penetrating keratoplasty for pseudophakic bullous keratopathy after extracapsular cataract extraction. Corneal edema occurred an average of eight months after cataract surgery (range, zero to 32 months). Of 17 corneal grafts, 16 (94%) have remained clear during an average follow-up period of 14 months (range, two to 32 months). One eye had a nonimmunologic graft failure. Of 16 eyes with clear grafts, 14 (87%) achieved a visual acuity of 20/40 or better after surgery. Two eyes with a visual acuity of 20/50 and 20/200 had opacified posterior capsules and one demonstrated age-related macular degeneration. One eye with a postoperative visual acuity of 20/40 demonstrated cystoid macular edema. Fifteen of 17 contralateral eyes showed slit-lamp evidence of endothelial dystrophy.

Endothelial survival in corneal tissue stored in M-K medium.

Cat corneas were stored at refrigerator temperatures in M-K medium (TC-199, 5% dextran), modified M-K medium (TC-199, 1% chondroitin sulfate), or on the intact globe in moist chambers for intervals of one to nine days. Less than 5% of the endothelial cells stained with trypan blue in corneas stored one to four days, regardless of the method of storage. In contrast, after five days, 20% or more of the cells took up the stain in 17 to 21 corneas stored in M-K medium. Although stain uptake indicated nonviability of cells, most of the endothelial cells remained structurally intact when observed by scanning and transmission electron microscopy unless the corneas were incubated in fresh TC-199 for two hours at 35 degrees C before trypan blue staining. In that case, the percentages of disrupted cells observed at each time interval correlated with the percentages of cells that had stained in each cornea. These results indicated that storage in M-K medium did not extend the time donor coreas can be stored before transplantation beyond four days.

Corneal edema and the intraocular use of epinephrine.

Commercially prepared dilutions (1:10,000) of epinephrine can cause marked increases in corneal thickness and loss of corneal endothelial cells when injected into the anterior chamber of the eye. Endothelial toxicity is related to the buffer capacity of the epinephrine solution, which is in turn controlled by the concentration of the antioxidant (sodium bisulfite) as well as by the vehicle formulation and a low pH value.

Accuracy of glaucoma detection with frequency-doubling perimetry.

PURPOSE: To determine the accuracy of glaucoma detection by frequency-doubling perimetry. METHODS: Stereoview optic nerve photographs, visual field examination, intraocular pressure measurements, medical and ocular history, and a screening and full threshold frequency-doubling perimetry examination were performed in a prospective study of consecutive subjects. Inclusion criteria included age of 45 years or older, absence of ocular disease other than glaucoma, cataract, or mild drusen, and Snellen visual acuity of 20/60 or better. A total of 125 eyes in 102 glaucoma subjects and 95 eyes of 95 normal subjects were included. Each eye was classified as "normal," "glaucoma," or "uncertain" by each of three ophthalmologists on the basis of all available clinical information with the exception of frequency-doubling perimetry results. Those in the glaucoma group were subclassified as having early (n = 51), moderate (n = 42), or severe (n = 32) glaucoma on the basis of automated Humphrey visual field criteria. In the glaucoma group, two eyes from a subject were allowed to be included (23 of 102 subjects) if they differed in level of damage because they were never analyzed within the same statistical analysis. RESULTS: Several diagnostic algorithms were evaluated. Algorithms based on the most depressed single point, pair of adjacent points, and cluster of three points performed nearly identically. For the screening test, if any abnormality was identified, specificity was 95%, whereas sensitivity was 39%, 86%, and 100% for early, moderate, and severe glaucoma, respectively. For the full threshold test, with at least one point depressed to the P < 0.5% level, specificity measured 91%, whereas sensitivity was 35%, 88%, and 100% for early, moderate, and severe glaucoma, respectively. The two global indices, mean deviation and pattern standard deviation, were also evaluated and were generally less accurate. CONCLUSION: Frequency-doubling perimetry, which is rapid and easily administered, is effective at detecting moderate and severe disease and appears well suited for glaucoma screening.

Diabetic keratopathy as a manifestation of peripheral neuropathy.

In a study of 102 patients (64 women and 38 men; 63 whites and 39 nonwhites; 77 with adult-onset disease and 25 with juvenile-onset disease), the data, after being adjusted for age, showed that diabetic peripheral neuropathy was associated with diabetic keratopathy. The strongest predictor of both keratopathy and corneal fluorescein staining was vibration perception threshold in the toes (P less than .01); the severity of keratopathy was directly related to the degree of diminution of peripheral sensation. Other predictors of keratopathy were reduced tear break-up time (P less than .03), the type of diabetes (P less than .01), and metabolic status, shown by fasting C-peptide levels (P less than .01). No significant relationships were found between keratopathy and tear glucose levels, endothelial cell densities, corneal thickness, or duration of disease.

The effects of sodium hyaluronate, chondroitin sulfate, and methylcellulose on the corneal endothelium and intraocular pressure.

Sodium hyaluronate (Healon), chondroitin sulfate, and methylcellulose have been used to protect the corneal endothelium from intraocular lens trauma. A study of the efficacy and toxicity of these compounds showed that 1% sodium hyaluronate, 0.4% methylcellulose, and 20% chondroitin sulfate were nontoxic to the corneal endothelium, but that 20% chondroitin sulfate caused a marked decrease in corneal thickness because of its hypertonicity. Anterior chamber injection of these viscous substances resulted in an increase in intraocular pressure. Within one to four hours the maximum intraocular pressure with 1% sodium hyaluronate was 67 +/- 4.1 mm Hg and that with 20% chondroitin sulfate was 55 +/- 3.5 mm Hg. The intraocular pressure did not increase to these high levels with 10% chondroitin sulfate or 0.4% methylcellulose or when the test substances were washed out of the anterior chamber. The corneal endothelium was protected from injury with 1% sodium hyaluronate and 20% chondroitin sulfate, but 10% chondroitin sulfate and 0.4% methylcellulose provided only minimal protection.

Keratomycosis in Wisconsin.

Candida albicans was the most common fungus responsible for mycotic keratitis in our series from a northern climate, as opposed to southern climates where other fungi were more common. Pimaricin was effective in our patients with Candida infections and in one patient with Aspergillus infection that had been unresponsive to previous amphotericin B.

Pseudophakia and intraocular pressure.

We studied the change in intraocular pressure in 373 consecutive eyes undergoing cataract extraction with intraocular lens implantation between Jan. 1, 1981, and May 31, 1982. There was a mean increase in intraocular pressure of 0.1 mm Hg following this surgery. This increase, however, was not statistically significant (P greater than .5). There was a mean rise in pressure of 0.8 mm Hg in the eyes undergoing intracapsular surgery and a mean fall in pressure of 0.6 mm Hg in the eyes undergoing extracapsular surgery (P less than .05). The change in pressure was unrelated to age, surgeon, or lens type. The results of a separate analysis of 16 eyes with a preoperative diagnosis of glaucoma and eight eyes with ocular hypertension were similar.

Corneal endothelial changes in type I and type II diabetes mellitus.

Forty-six corneas from 25 patients who had had type II (adult-onset) diabetes for more than ten years were examined by specular microscopy with quantitative morphometric analyses of individual endothelial cells. Thirty-four corneas from 21 age-matched nondiabetic subjects were examined for comparison. We also examined 31 corneas from 17 patients with type I (juvenile-onset) diabetes and compared them to 41 corneas from 23 age-matched normal volunteers. The corneal endothelium in type II diabetes showed no difference in cell density but demonstrated a significantly higher coefficient of variation, a decrease in the percentage of hexagonal cells, and a low figure coefficient compared to an age-matched nondiabetic population. Type I diabetes produced similar cell changes, but these changes occurred in the earlier decades. Moreover, we detected a significantly higher rate of cell loss in type I diabetes, resulting in a significant decrease in cell density in the fourth and fifth decades. These results clearly indicate that the diabetic endothelium is morphologically abnormal. The observed anatomic changes result in a less stable and more vulnerable cell layer, possibly explaining some of the persistent clinical changes in the diabetic cornea after surgical trauma.

Adenine arabinoside in idoxuridine unresponsive and intolerant herpetic keratitis.

Twenty-two patients with active herpes simplex dendritic keratitis, in whom topical idoxuridine was unsuccessful in controlling their disease, were treated with topical adenine arabinoside (ara-A), a purine analogue effective against many DNA viruses. This drug was an effective antiviral agent in these patients. No signs of ocular or adnexal toxicity were noted.

Comparative toxicity of intraocular irrigating solutions on the corneal endothelium.

Isolated rabbit and human corneas were perfused in vitro with Plasma-lyte 148 solution and with a glutathione bicarbonate Ringer's solution. The corneal swelling rate and ultrastructure were compared to corneas perfused with three commonly used intraocular irrigating solutions. Corneas perfused with Plasma-lyte 148 swelled at a rate of 47 mu/gr and the endothelial cells separated from each other and showed extensive damage after three hours of perfusion. By comparison, corneas perfused with 0.9% NaCl increased in thickness by 98 mu/hr, lactated Ringer's by 39 mu/hr, balanced salt solution by 24 mu/hr, and glutathione bicarbonate Ringer's solution by 4 mu/hr. These results indicate that endothelial cell damage and increased corneal thickness observed during perfusion was related to the incomplete composition of 0.9% NaCl, Plasma-lyte 148, and lactated Ringer's and that endothelial cell damage can be prevented if the intraocular irrigating solution contains concentrations of inorganic and organic constituents that are similar to those in aqueous humor.