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The histopathologic findings in a case of ocular invasion in rhinocerebral mucormycosis are described. The findings of hyphae in the inner sclera and marked involvement of the posterior ciliary arteries suggested an arterial route of ocular invasion by fungus. Only five other cases of rhinocerebral mucormycosis with ocular fungal invasion have been reported to our knowledge. All six patients died from the infection. As a group, these cases suggest that the presence of ocular infiltration by fungus may indicate poor prognosis in rhinocerebral mucormycosis.

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.

The incidence of late-onset bleb-related endophthalmitis was evaluated retrospectively in 229 consecutive trabeculectomies performed with adjunctive 5-fluorouracil (5-FU) therapy. Mean follow-up was 23.7 +/- 16.3 months (range, 3 to 60 months). Thirteen eyes (5.7%) of 11 patients developed bleb-related endophthalmitis an average of 25.9 +/- 17.4 months (range, 5 to 58 months) after surgery. Infection occurred in 9 of 96 (9.4%) procedures performed from below and in 4 of 133 (3.0%) procedures performed superiorly (P = 0.05, Fisher's exact test). The relative risk of bleb-related endophthalmitis in trabeculectomy from below versus above is 4.0 after adjustment for age and sex (95% confidence interval = 1.1, 14.8). Trabeculectomy with adjunctive 5-FU performed from below carries an increased risk of late bleb-related infection. The incidence of late bleb-related endophthalmitis after 5-FU trabeculectomy appears to be higher than that for trabeculectomy without adjunctive 5-FU injections.

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.

PURPOSE A 90-year-old woman was referred to us with a 1-month history of progressively worsening blepharoconjunctivitis. She had a complete acquired ankyloblepharon of the right lids, which resulted in the appearance of a right upper lid abscess on computed tomography. METHODS Blepharotomy with separation and debridement of the lid margins was performed. RESULTS Cultures were positive only for herpes simplex virus, type II. CONCLUSIONS Herpes simplex blepharoconjunctivitis may take many clinical forms. Our patient's severe manifestations led to the clinical and radiologic appearance of preseptal cellulitis with a right upper lid abscess.

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

• Chronic Aspergillus meningitis and cerebral vasculitis occurred in a 67-year-old man. He experienced periorbital pain that increased in severity during a tenmonth period. Although no focal neurologic deficits were initially present, oculosympathetic paresis, corneal hypesthesia, and optic neuropathy developed. This is the first report, to our knowledge, of paratrigeminal syndrome with optic neuropathy due to aspergillosis. The case was also unusual because it was chronic and there was no extracerebral infection or predisposing factors, such as underlying malignancy or collagen vascular disease.

NMR pulse sequences have been investigated which selectively suppress undesired signal components from multiple-exponential spin-spin and spin-lattice relaxation curves. Suppression is achieved by exploiting differences in the relaxation times of sample components. Special attention is devoted to discussion of practical details necessary for implementation of these methods, as well as their relative advantages and disadvantages. The techniques are illustrated using multiple-compartment aqueous phantoms and are then employed in measurements of proton T1 and T2 values for freshly isolated guinea pig lenses immersed in aqueous buffer solutions to prevent dehydration and maintain viability. These methods obviate many of the difficulties inherent in obtaining accurate relaxation times for minor components of multiple-exponential curves and should be useful in many applications of NMR to the study of intact tissue, both in vitro and in vitro. © 1986 Academic Press, Inc.

A full-term, 2,828-g male infant who lived five weeks had histologically proven, bilateral, congenital anophthalmos. The infant had multiple congenital anomalies including esophageal atresia, choanal stenosis, tetralogy of Fallot, persistent left superior vena cava, arhinencephaly, retardation of myelination in the brain, cerebellar sclerosis, and dysplasias, as well as other developmental anomalies of the central nervous system. There was no family history of anophthalmos, and, in view of the arhinencephaly, we diagnosed sporadic secondary anophthalmos.

We reviewed 17 cases of inverted follicular keratosis. The median age of the patients at the time of surgery was 69 years. Follow-up in 14 cases showed no recurrences of inverted follicular keratosis, which is a benign skin lesion, often mistaken clinically and pathologically for a malignancy. Inverted follicular keratosis is characterized histologically by the presence of squamous eddies, acantholysis, acanthosis, and hyperkeratosis.

Recently, patients with visual paraneoplastic syndrome (VPS) were described, a binocular loss of vision found in patients with small cell carcinoma of the lung (SCCL). The patients have serum antibodies against a small number of discrete antigens which are shared by the retina and small cell carcinoma cells, and which are associated with cells and processes of the ganglion cell layer of the retina. Pathologic findings are presented with regard to the presence of immunoglobulins in, and the nature of the lesions in, the central nervous system of a VPS patient. The patient's blood-brain barrier was shown to be compromised, as demonstrated by the finding of high immunoglobulin levels in the cerebrospinal fluid and immune deposits in the retina. It is further shown that within the central nervous system only the retina and optic nerve show any tissue damage with the specific loss of retinal ganglion cells and their processes. The findings support the hypothesis of an autoimmune cause for this remote effect of cancer.

Chez un malade explore pour laceration oculaire, la tomodensitometrie rectifie le diagnostic de l'echographie A: il s'agit d'une bulle d'air dans le segment anterieur

Immunoreactive atrial natriuretic peptide (ANP) has been detected in retinal tissue by radioimmunoassay, although it is unclear whether it was in retinal cells or represented residual peptide from blood and/or ocular fluids. We report here, using the immunoperoxidase method and a highly specific anti-rat ANP, that the peptide was localized consitently in the outer and inner plexiform layers of retinas of rats and rabbits. This information raises important issues: what are the implications for retinal function and, since blood-borne radioligands do not reveal retinal ‘receptors’, what is the endogenous target of retinal ANP?

The Fukuyama form of congenital muscular dystrophy (FCMD), first described in Japan, is associated with distinct dysplastic cerebral malformations including agyria and micropolygyria of cerebral cortex, micropolygyria of cerebellum, and leptomeningeal gliomesodermal proliferations. We describe seven cases in four families from the United States with a syndrome similar to FCMD but with additional ophthalmic malformations. We believe that these cases represent a form of congenital muscular dystrophy different from FCMD and termed it cerebro-ocular dysplasia-muscular dystrophy (COD-MD) syndrome.

To the Editor. —There is a need in medical education for a simulator on which students and residents can practice the basic skills of ophthalmoscopy. Considerable time would be saved and patient discomfort and inconvenience reduced if the basic skills of ophthalmoscopy could be learned using a practical, inexpensive model system. Although model eyes do exist, they contain significant limitations. For example, some models depend on handpainted reproductions of pathologic findings as rendered on the posterior internal surface of the model.1There is no flexibility to examine various fundus disorders without purchasing several models. One model uses slide transparencies of the viewing object, resulting in decreased resolution of fundus detail secondary to the inherent "graininess" of such transparencies.2Finally, other models are too complex or expensive, such as one eye model that contains a photosensitive pupil that dilates in response to mydriatic eye drops.3 We have developed

• A 74-year-old woman was found to have increasing proptosis in a blind, painful left eye with neovascular glaucoma. Uveal malignant melanoma with massive orbital involvement was diagnosed, and the patient underwent orbital exenteration, with preoperative and postoperative orbital irradiation. The tumor was a mixedcell, diffuse uveal malignant melanoma with involvement of the optic nerve adjacent to the line of surgical transection and of the optic nerve sheath. Subsequently, the cerebrospinal fluid cytology disclosed cells consistent with malignant melanoma, despite the absence of neurologic signs or symptoms. Cerebrospinal fluid cytology is essential in such cases, and ultrasonography is of value.

The interactions between rabbit corneal epithelium and endothelium were investigated in an organ culture model using scanning electron microscopy and correlative light microscopy. Following mechanical removal of corneal endothelium, corneal epithelium was observed to migrate across the cut surface of the corneal stroma and onto the denuded Descemet's membrane after 48 hours in organ culture. By 72 hours, a distinct line of contact between the migrated epithelium and endothelium was established. Following epithelialendothelial contact, no cellular migration occurred. Corneal endothelial inhibition of epithelial migration may be a major factor in the prevention of surface epithelial invasion and proliferation following surgery and trauma.

We examined a family pedigree in which retinitis pigmentosa and hemophilia A were inherited in an X-linked manner. Six female carriers were identified by electroretinography. Results of ophthalmoscopic examination were normal in two women, while four displayed marked variability in phenotypic expression. Six of seven males identified with retinitis pigmentosa had hemophilia A. One asymptomatic boy had a markedly abnormal electroretinogram despite normal ophthalmoscopic examination. Pedigree analysis showed a high recombination rate, which would be expected as these two genes are known to be at opposite arms of the X chromosome.

The neuropathologic and ophthalmopathologic findings in a 53/4-year-old boy with Alexander's disease are reported. Light- and electron-microscopic and immunohistochemical studies revealed that (1) the granular osmiophilic deposits (GOD) in Alexander's disease accumulate mainly in astrocytic processes to form Rosenthal fibers, (2) the Bergmann glia are different in this regard and accumulate the deposits primarily in their perikarya, (3) the Muller cells of retina (which closely resemble astrocytes) do not accumulate GOD, (4) the deposits are also not present in other glial cells and glial-like cells such as pituicytes and pineocytes, (5) the deposits are sparse in the retrobulbar optic nerves, and (6) the peroxidase-antiperoxidase and immunofluorescence studies did not demonstrate glial fibrillary acidic protein (GFAP), albumin, immunoglobulins, or fibrinogen in the astrocytic deposits. The differential deposition of GOD in various cytoplasmic regions of astrocytes in different areas of central nervous system (CNS) suggests that astrocyte metabolism may not be uniform throughout the brain. Attention to this point may prove helpful in understanding the pathogenesis of the deposits in Alexander's disease. The absence of immunohistochemically demonstrable plasma proteins and GFAP in the astrocytic GOD indicates that the latter have an origin different from plasma proteins and glial filaments. Alternatively, the deposits may be derived from these proteins, but their antigenicity has since been altered.

Nineteen blind eyes enucleated for painful angle closure-glaucoma secondary to iris neovascularization (rubeosis iridis) were examined by scanning electron microscopy and correlative light and transmission electron microscopy. Fresh and deparaffinized tissue from patients with diabetes mellitus, central retinal vein occlusion, and retinoblastoma were studied. Scanning electron microscopy revealed extensive peripheral anterior synechia formation and flattening and effacement of the anterior iridic surface by a confluent fibrovascular membrane. New vessels on the anterior iris uniformly were hidden beneath a clinically inapparent, superficial layer of myofibroblasts, ie, fibroblastic cells with smooth muscle differentiation. Myofibroblasts may provide the motive force for synechial closure and ectropion iridis in neovascular glaucoma.

ronts have many organisms. The multinucleate meronts of References the organisms in the calf are distinct from Toxoplasma and Besnoitia, because the latter divided by endodyogeny (division into two). No species of Isospora has been known to develop in tissues of ruminants (cattle, sheep, goat^).^ Thus, by exclusion, the organism may be Eimeria, although sexual stages were not seen. Lesions in the present study were considered to be due to the coccidium because the infection was localized in the small bile ducts and protozoa were seen in lesions. Moreover, the hepatobiliary lesions were similar to those caused by Eimeria hiepei in mink3 and Eimeria stiedae in rabbits.’ Intestinal coccidiosis due to Eimeria is among the most common of parasitic infections of cattle, sheep, and goats.5 Although species of Eimeria occasionally invade the gallbladder of goats’ and mesenteric lymph nodes of sheep and goats,6 none have been reported to do so in cattle. The parasite of cattle in the present case was similar to that in the gallbladder of a goat, but sexual stages were not observed.

\s=b\Chronic Aspergillus meningitis and cerebral vasculitis occurred in a 67-year\x=req-\ old man. He experienced periorbital pain that increased in severity during a tenmonth period. Although no focal neurologic deficits were initially present, oculosympathetic paresis, corneal hypesthesia, and optic neuropathy developed. This is the first report, to our knowledge, of paratrigeminal syndrome with optic neuropathy due to aspergillosis. The case was also unusual because it was chronic and there was no extracerebral infection

The disposable skin biopsy punch is an excellent instrument for excisional biopsy of tarsal conjunctival lesions.