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Objective To determine if topical application of naltrexone hydrochloride (NTX), an opioid antagonist, restores tear production and corneal sensation in rats with diabetes mellitus. Methods Type 1 diabetes was induced with streptozotocin in rats. Tear production was measured by the Schirmer test, and corneal sensitivity, by an esthesiometer. Eye drops of 10 −5 M NTX or sterile vehicle were administered either once only or 4 times a day for 1 or 5 days; a single drop of insulin (1 U) was given once only. Results Dry eye and corneal insensitivity were detected in the diabetic rats beginning 5 weeks after streptozotocin injection. One drop of NTX or 4 times a day for 1 or 5 days reestablished tear production and corneal sensitivity within 1 hour of administration. The reversal of dry eye lasted for up to 2 to 3 days depending on drug regimen, but restitution of corneal sensation lasted for 4 to 7 days. Topical application of 1 eye drop of insulin restored corneal sensitivity within 1 hour and lasted for at least 2 days. In contrast, 1 eye drop of insulin did not increase tear production at 1, 24, or 48 hours compared with diabetic animals receiving sterile vehicle. Conclusion Topical treatment with NTX normalizes tear production and corneal sensitivity in type 1 diabetic rats. Clinical Relevance Topical application of NTX to the ocular surface may serve as an important strategy for treating dry eye and corneal anesthesia in diabetes. Its effect, if any, in other forms of decreased corneal sensitivity and/or dry eye should be investigated.

Objective To determine whether topical application of naltrexone prevents exuberant granulation tissue formation with neovascularization in diabetic rat corneas. Methods Diabetes was induced with streptozotocin. A 5-mm corneal abrasion at 9 or 11 weeks was treated topically for 7 days (4 times daily) with naltrexone or a sterile vehicle. Results Within 2 to 5 days after reepithelialization, diabetic rats given the sterile vehicle had a 41% incidence of corneal lesions represented by exuberant granulation tissue with corneal neovascularization extending from the limbus. These lesions exhibited edema, cellular and vascular inflammation, and disruption of stromal lamella by fibrovascular tissue and calcium mineralization, but infection was not detected. No corneal lesions were recorded in the diabetic group treated with naltrexone or the control group given the sterile vehicle. Diabetic rats with corneal lesions given the sterile vehicle reepithelialized more slowly than diabetic rats given the sterile vehicle without such lesions, but no difference in blood glucose levels were noted. Conclusions Using a minimally invasive model in diabetic rats, topical naltrexone normalizes corneal wound healing and prevents neovascularization. Clinical Relevance Direct application of naltrexone may serve as an important strategy for facilitating corneal healing and inhibiting corneal neovascularization.

Objective To determine whether topical application of insulin normalizes delayed corneal wound healing in rats with diabetes mellitus (DB). Methods Diabetes mellitus was induced with streptozocin. A 5-mm corneal abrasion at 9 or 11 weeks was treated topically for 7 days (4 times daily) with 1, 2, or 5 U of insulin or with sterile vehicle (SV). Results Residual corneal epithelial defects of rats with DB receiving SV (hereafter called DB SV rats or animals) were approximately 35% larger than in healthy animals receiving SV (hereafter called healthy SV rats or animals). Rats with DB receiving topical insulin had wounds ranging from 19% to 60% smaller than DB SV rats, corresponding to wound sizes in healthy SV rats. Topical insulin had no effect on reepithelialization of corneal wounds in healthy SV rats. Insulin did not affect corneal thickness, ocular pressure, or serum glucose level. The corneal sensitivity of DB SV rats was markedly reduced from healthy SV rats, but rats with DB given insulin had corneal sensitivity values comparable to the healthy SV group. DNA synthesis was decreased in DB SV corneal epithelium but was comparable to that in healthy SV rats after they received insulin; apoptosis and necrosis levels were similar in all groups. Conclusion Topical insulin normalizes corneal reepithelialization in diabetic rats. Clinical Relevance Direct application of insulin may serve as an important strategy for treating diabetic keratopathy.

Objective To determine whether molecular manipulation of the opioid growth factor receptor (OGFr) alters corneal reepithelialization following central corneal abrasion in rats. Methods The plasmid pcDNA3.1 + OGFr, carrying the rat OGFr complementary DNA in both the sense and antisense orientations, and empty vector (EV), were delivered by gene gun to the rat cornea. After 24 hours, corneas were abraded and reepithelialization was documented by fluorescein photography. Twenty-four hours after wounding, DNA synthesis (with bromodeoxyuridine) was examined. Results Eyes transfected with sense constructs of OGFr had corneal defects that were 24%, 52%, and 50% larger than the EV group at 16, 24, and 28 hours, respectively. Conversely, corneas transfected with antisense constructs of OGFr had corneal defects that were 56% and 48% smaller than the EV group at 16 and 24 hours, respectively. Bromodeoxyuridine labeling in the basal and suprabasal layers of the antisense group were increased 3.3- and 3.7-fold, respectively, in DNA synthesis from corresponding EV layers; DNA synthesis was comparable in the sense and EV groups. Conclusions Excess OGFr delays reepithelialization, whereas attenuation of OGFr accelerates repair of the corneal surface. Clinical Relevance Inhibition of opioid growth factor action using gene therapy could be important in the treatment of corneal diseases such as nonhealing and recurrent erosions, diabetic keratopathy, and neurotrophic keratitis.

Objective: To describe the phenotypic variation exhibited by members of families with combined granularlattice (Avellino) corneal dystrophy. Setting: We examined 40 patients (age range, 12 to 85 years) from six unrelated families with Avellino corneal dystrophy. This included the first individuals to ever be examined near the presumed site of origin in Italy. In addition, one family was the first to trace its origins to Germany rather than to Italy. We studied the phenotypic expression of the disease in the cornea, visual acuities, subjective complaints, complications, treatment, and histologic condition of these individuals. Results: The granular stromal lesions reach their mature quantity and size early in life, and appear as either gray and crumb-shaped deposits or superficial with an annular and planar distribution. The lattice component appears gradually, beginning and maturing later in life. The phenotypic variation within families was found to be substantial. Widely variable proportions of lattice and granular changes were found within single sibships. Visual acuities ranged from 20/20 to 20/400. Recurrent corneal erosions were present but infrequent. Subjective complaints included glare and decreased night vision. Penetrating keratoplasty was required in one individual to restore vision. Histopathologic examination revealed typical amyloid and granular deposits. Granular deposits were found replacing Bowman's membrane and extending to the corneal surface. These deposits probably represent the cause of recurrent erosions. Conclusions: Combined granular and lattice corneal dystrophy may present with substantial phenotypic variation. The disease can be found in individuals who trace their ancestry to both Italy and Germany, a wider geographic distribution than previously proposed.

• A 35-year-old man with a history of repeated previous facial injuries presented with acute onset of a right orbital mass less than 2 weeks after blunt trauma to the right eye. Orbital B-scan ultrasonography and computed tomography showed an intraconal cystic lesion. The tumor was excised via lateral orbitotomy. Pathologic evaluation demonstrated a hematic cyst containing fresh blood. The presence of hemosiderin in the cyst wall suggested recent bleeding in a preexisting orbital hemorrhagic lesion. Patients with hematic cysts of the orbit usually present with a subperiosteal mass months to years after trauma.

This book, published in French and English, is a compendium of presentations by 16 noted authorities on the optic disc and glaucoma given at a symposium in June 1989 in Angers, France. Among the authors were Stephen Drance, Josef Flammer, Jost Jonas, and Bernard Schwartz. Seldom has there been such an opportunity for seminal knowledge to be disseminated on a most vexing clinical problem. However, this major educational opportunity was hindered by poor layout and editing. This bilingual book allows English-speaking students to test their knowledge in translating French prose. Unfortunately, the articles are not translated simultaneously in parallel columns, but are arranged in segments that jump schizophrenically between languages. For example, a beautiful biographic tribute to Albrecht von Graefe by Pierre Amalric begins in French on page 11, switches to English on page 12, resumes in French on page 13, continues in English on pages 17 and 18

To the Editor. —I was pleased to read the report by Warren and associates1describing their experience with the disposable skin biopsy punch. In 1981, we described the use of an essentially identical instrument, the Baker's disposable biopsy punch, for obtaining tarsal conjunctival biopsy specimens.2 Since our initial report, we have modified our procedure. The biopsy "button" is outlined using the Acuderm punch described by Warren and associates. (We have discontinued use of the Baker's punch due to its unavailability.) As the biopsy specimen is outlined, the punch penetrates the tissue to the desired depth. A suture is passed through the base of the specimen and used to provide traction as the biopsy button is amputated at its base with fine scissors or a scalpel. After the needle is safely disposed of, the specimen is permitted to remain on the suture during fixation to facilitate specimen identification, orientation

"Orbital pathology represents the no-person's land of ophthalmology." For those who would agree with this statement and who have been lost in an area filled with confusing terminology, Dr Shields provides a road map and a sense of order. From his preface onward, the author provides a clear and concise approach to orbital lesions. The book is divided into three sections: "Basic Considerations," "Primary Tumors," and "Metastatic and Secondary Orbital Tumors." Each section fulfills its responsibilities admirably. "Basic Considerations" leads the reader through orbital anatomy, a discussion of proptosis, and the basic principles of clinical evaluation, laboratory diagnosis, and treatment of orbital lesions. Inflammatory lesions that may simulate true neoplasms are also discussed. "... the author's vast clinical experience permits him to speak authoritatively..." The remaining two sections discuss specific neoplasms. The lesions are considered from the perspectives of definitions and incidence, clinical features, diagnostic approaches, histopathology and pathogenesis, management, and