Tyrosinemia type II: nine cases of ocular signs and symptoms.

PURPOSE: To report nine cases of tyrosinemia type II, with ocular signs and symptoms. METHODS: Participants included nine patients (18 eyes) who were followed for a mean follow-up period of 6.5 years (range, 2 to 8 years). Intervention included dietary restriction of tyrosine and phenylalanine, which led to resolution of ocular and cutaneous lesions, improved behavior in one patient, and may have prevented developmental delay in others. The main outcome measures were visual acuity and serum tyrosine levels to determine the response to dietary therapy. Intelligence testing and developmental screening were performed when appropriate. RESULTS: All patients presented with ocular signs and symptoms as the primary manifestation of disease and serve to illustrate the typical ocular findings of this syndrome. Three patients presented with cutaneous manifestations, and one patient had mild mental impairment at the time of diagnosis. CONCLUSIONS: Recalcitrant pseudodendritic keratitis may be the presenting sign in tyrosinemia type II. Awareness of the presenting signs and symptoms may accelerate the diagnosis and dietary intervention. Initiation of a tyrosine-restricted and phenylalanine-restricted diet in infancy is most effective in preventing cognitive impairment.

Influence of degradation on binding properties and biological activity of endomorphin 1.

The recently-isolated endogenous peptide endomorphin 1 has high affinity for the mu opioid receptor and plays an important role in analgesia. Several of its degradation products have been isolated from the central nervous system. Degradation products present structural similarities and may influence the receptor binding properties and biological activity of the parent compound. Therefore, we investigated how degradation of endomorphin 1 might influence ligand binding to the mu opioid receptor, the consequent activation of G proteins and its antinociceptive effect. Both N- and C-terminal truncation of endomorphin 1 resulted in peptides presenting considerably lower opioid receptor binding potency. None of these peptides had an effect on GTP binding, nor was able to produce analgesia, suggesting that degradation destroys the biological activity of endomorphin 1.

The management of corneal trauma: advances in the past twenty-five years.

Over the past quarter century, advances in our understanding of corneal anatomy, physiology, and wound healing have all played an integral role in the management of corneal trauma. As the etiologies of corneal trauma have changed, so has our understanding of the impact of injury on corneal function as it relates to visual rehabilitation. Numerous new classes of antibiotics, antiinflammatory agents, and tissue adhesives have emerged. Occlusive therapy has advanced from simple pressure patching bandage soft contact lenses and collagen shields. Surgical instrumentation, operating microscopes, viscoelastic substances, and suture materials have all improved the outcomes of corneal trauma repair. Improved understanding of the refractive properties of the cornea through topography and alternative suture techniques has helped us restore the natural corneal curvature and visual outcomes. Consequently, in the last quarter of this century our therapeutic approaches to cornea trauma, both medical and surgical, have improved.

Pituitary adenylate cyclase-activating polypeptide induces hyperthermia in the rat.

The effects of centrally administered pituitary adenylate cyclase-activating polypeptide (PACAP-38) on body temperature were investigated in rats. Intracerebroventricular (i.c.v.) administration of PACAP-38 in doses of 500 and 1000 ng induced a dose-related elevation in colon temperature 2, 3, 4, 5 and 6 h after injection. The i.c.v. pretreatment of the animals with different dilutions of PACAP-38 antiserum prevented the development of hyperthermia in PACAP-38-treated animals, whereas PACAP-38 antiserum alone did not modify the colon temperature. An intramuscular injection of noraminophenazone (a cyclooxygenase inhibitor) abolished the PACAP-38-induced hyperthermia. Our data indicate that PACAP may induce hyperthermia via the central nervous system, and this hyperthermic effect may be mediated via a cyclooxygenase-involved pathway.

Management of oculus fragilis in Ehlers-Danlos type VI.

PURPOSE: To describe an alternative, novel surgical approach to the repair of a ruptured globe in the second reported patient with keratoglobus, Ehlers-Danlos type VI, and normal lysyl hydroxylase. METHODS: Under general anesthesia, a 360 degrees conjunctival peritomy was performed and the epithelium was removed from the keratoglobus cornea. Descemet's membrane and endothelium were removed from a fresh donor corneoscleral ring. An onlay epikeratoplasty was then performed and the entire donor corneoscleral button was secured to the sclera with 9-0 nylon suture. The conjunctiva was brought into position and tacked down over the edge of the donor graft. After 4 months, a full-thickness penetrating keratoplasty was then performed. RESULTS: The patient ultimately had a ruptured globe in the fellow eye and thus required the identical procedure OU. Both eyes were successfully repaired with a final visual acuity OU of 20/100. CONCLUSION: The described surgical approach allowed successful surgical repair of bilateral ruptured globes in a patient with keratoglobus, Ehlers-Danlos type VI, and normal lysyl hydroxylase levels. In the previous report of such a patient by Judisch et al. (1), the attempt at surgical repair was unsuccessful and ended in enucleation. The described surgical technique may be used to treat advanced keratoglobus or oculus fragilis.

Long-lasting antinociceptive effect of DAMGO chloromethyl ketone in rats.

Previously, the opioid peptide Tyr-D-Ala-Gly-(NMe)Phe-CH2Cl (DAMCK) has been shown to bind irreversibly to mu opioid receptors in vitro. In the present work, the antinociceptive effect of DAMCK has been evaluated. Rats treated systemically with DAMCK (1-100 pg/kg) displayed a dose-dependent increase in tail-flick analgesia that peaked by 15 min, then stayed about the same until 60 min, followed by some decrease over time. Higher doses of DAMCK (10 ng/kg-100 microg/kg) produced a near-maximal antinociceptive effect that remained stable for 4 h. Significant antinociception was still detected 8 h, but not 24 h postinjection. In comparison, the parent peptide DAMGO (Tyr-D-Ala-Gly-(NMe)Phe-Gly-ol) reached maximal effect by about 30 min, followed by a rapid cessation of its antinociceptive response. Naloxone administered before DAMCK antagonized the antinociceptive response of DAMCK, indicating that it was mediated via opioid receptors. Naloxone administered 45 min after DAMCK attenuated the tail-flick response to some extent, but a substantial part (40-60% depending on the peptide concentration and evaluation time) remained unaffected. Central administration of DAMCK also elicited time- and concentration-dependent, profound, opioid receptor mediated, apparently irreversible antinociception.

Obesity as a factor in penetrating keratoplasty.

PURPOSE: We reviewed the clinical data on 10 obese patients to define the role of obesity as a factor for consideration in planning penetrating keratoplasty. METHODS: We performed a retrospective case series review of penetrating keratoplasty in obese patients. RESULTS: In our series of 10 patients, spontaneous extrusion of lens and vitreous (three patients) and choroidal hemorrhage (one patient) were intraoperative complications. Wound leakage, wound dehiscence (two patients), iridocorneal synechia formation, and graft rejection (one patient) were postoperative complications. Despite these complications, seven of the 10 patients achieved a final postoperative visual acuity of > or =20/30. CONCLUSION: Cornea surgeons must consider obesity as a potential risk factor that may be mitigated partially by careful preoperative patient evaluation, anesthesia planning, and meticulous attention to patient positioning and comfort during surgery.

Staphylococcal endophthalmitis following cataract extraction in a patient with Darier's disease.

PURPOSE: To report staphylococcal endophthalmitis following cataract extraction in a patient with Darier' s disease. METHODS: A 67-year-old man presented with decreased visual acuity OD and hypopyon 3 days status post-cataract extraction with intraocular lens placement. The patient was hospitalized and placed on topical and intravenous antibiotics. A diagnostic vitreous tap, pars plana vitrectomy, and intravitreal antibiotic installation were performed. RESULTS: Vitreal tap cultures indicated Staphylococcus epidermidis. His clinical status improved after vitrectomy and antibiotic therapy. The same bacteria was cultured from the patient's eyelids. CONCLUSIONS: The source of the S. epidermidis was the skin lesions on the patient's face and eyelids. Darier's disease is an exfoliative hyperkeratotic skin disease that affects all areas on the body except the buttocks. Although clean, sterile surgical techniques were followed, the risk of endophthalmitis following intraocular surgery in a patient with Darier's disease may be increased due to his or her dermatologic condition.

Repair of Descemet's membrane detachment with perfluoropropane (C3F8)

PURPOSE: To report the use of perfluoropropane (C3F8) gas in the repair of Descemet's membrane detachments. METHODS: Descemet's membrane detachments after cataract surgery in three eyes and pars plana vitrectomy in a fourth underwent anterior-chamber gas-exchange descemetopexy with an isoexpansile 14% mixture of C3F8 to facilitate reattachment of Descemet's membrane. RESULTS: Descemet's membrane detachment was successfully reattached after anterior-chamber gas exchange with 14% C3F8 in three of the four eyes treated. The fourth eye treated with 14% C3F8 probably failed Descemet's membrane reattachment because of an unrecognized viscoelastic bleb situated anterior to Descemet's membrane. No corneal decompensation or fluctuations in intraocular pressure were believed to be attributable to isoexpansile C3F8 gas exchange. CONCLUSION: Early recognition and repair of Descemet's membrane detachments may prevent complications, such as corneal decompensation, corneal opacities and edema, and an overall decline in visual acuity. Isoexpansile C3F8 is demonstrated as a safe and efficacious alternative for the repair of Descemet's membrane detachment.

Bilateral corneal ulcers in primary vitamin A deficiency.

PURPOSE: To report a case of bilateral corneal ulcers and perforations resulting from hypovitaminosis A in an alcoholic patient. METHODS: A 38-year-old cachetic man presented with bilateral corneal ulcerations and severe visual loss. He was hospitalized, developed bilateral corneal perforations, and was treated with bilateral corneal transplants. RESULTS: Serum vitamin A level was 0.01 microg/dL (normal, 0.30-0.75). The electroretinogram was consistent with vitamin A deficiency. His clinical status improved after vitamin A replacement. CONCLUSIONS: Although rare in developed countries, the ophthalmologist must consider avitaminosis A in the differential diagnosis of corneal ulcerations in cachetic, alcoholic, or chronically ill patients. Early diagnosis and treatment can prevent unwanted outcomes.

Vasoactive intestinal polypeptide induces analgesia and impairs the antinociceptive effect of morphine in mice.

Vasoactive intestinal polypeptide (VIP) has numerous regulatory roles in peripheral, endocrine organs and in the central nervous system. The present study related to the effects of centrally (intracerebroventricularly) administered VIP on pain sensitivity and on opiate tolerance and dependence in intact male CFLP mice. VIP was analgesic when administered alone centrally. Naloxone treatment abolished this analgesic effect. VIP decreased the analgesic effect of a single subcutaneous morphine injection and the development of chronic tolerance to morphine. Morphine withdrawal signs were not significantly affected after VIP pretreatment. These findings indicate that VIP may play a role in pain sensitivity and that an opiate component may participate in this effect.

Keratoconus and Turner's syndrome.

PURPOSE: To report the association of keratoconus and Turner's syndrome in three patients and to review the ophthalmic manifestations of Turner's syndrome. METHODS: Three patients with keratoconus and Turner's syndrome were identified and reported in a retrospective review. RESULTS: These three cases represent the first series of patients with keratoconus and Turner's syndrome. All three patients underwent penetrating keratoplasty with good visual rehabilitation. None of the patients had other ocular features associated with Turner's syndrome. CONCLUSION: Turner's syndrome is commonly associated with ocular problems. In this series we identify an association of keratoconus with Turner's syndrome. Clearly, a careful ocular examination in this condition with attention to ocular features of Turner's syndrome is important.

Small-diameter, round, eccentric penetrating keratoplasties and corneal topographic correlation.

PURPOSE: The purpose of the study is to report the outcome and postoperative topographic analysis of seven patients who underwent small-diameter, round, eccentric penetrating keratoplasty. METHODS: Seven patients underwent small-diameter, round, eccentric penetrating keratoplasty for a variety of corneal disorders (cataract wound necrosis and dehiscence or fistula, three patients; penetrating keratoplasty wound infection, two patients; corneal rheumatoid melt and perforation, one patient; localized fungal keratitis, one patient). Full-thickness corneal transplants ranged in size from 3.0 to 5.5 mm. The graft wound and sutures spared the visual axis in all cases. Patients were observed for 7 to 42 months (mean, 21 months). All patients had postoperative topographic analysis. One of these also had preoperative analysis. RESULTS: All grafts tectonically were effective in treating the intended condition. Best-corrected visual acuity was 20/30 or better in the four patients without pre-existing corneal transplants or dry eyes; 20/60 and 5/200 in the patients with previous central penetrating keratoplasties; and 20/40 in the patient with rheumatoid melt. There was no clinically significant regular or irregular astigmatism induced centrally by the eccentric graft in the four patients where visual acuity was 20/30 or better. Irregular astigmatism was noted in the other three patients. CONCLUSION: Small-diameter, eccentric penetrating keratoplasties may be used successfully to treat various peripheral corneal disorders. In some cases, this can be performed without inducing high or irregular astigmatism or both centrally.

OptiSol corneal storage medium and transmission of Treponema pallidum.

This study was conducted to provide experimental information on the probability of syphilis transmission resulting from corneal transplantation. To determine the effects of commonly employed corneal storage conditions on the survival and infectivity of Treponema pallidum, T. pallidum subsp. pallidum (Nichols) was inoculated into OptiSol storage medium or a T. pallidum survival medium at a concentration of 10(6)/ml and incubated in cornea viewing chambers for 24 h at 4 degrees C. When inoculated intradermally into rabbits (0.1 ml per site), none of the 10 sites developed lesions from suspensions incubated in OptiSol in the presence or absence of 100 microgram/ml gentamicin; T. pallidum incubated in the survival medium yielded lesions at one of 10 sites, whereas freshly extracted organisms produced lesions at all 10 sites. In another set of experiments, the infectivity of corneal tissue from rabbits inoculated intratesticularly with 2 x 10(7) T. pallidum 10 days earlier was determined. Corneas from five T. pallidum-infected rabbits were excised, extracted, and tested for infectivity either immediately after removal or after 24-h storage in OptiSol. Recipient rabbits developed lesions at five of 50 intradermal sites when the corneas were neither stored in OptiSol nor rinsed before extraction. Corneas from 10 donor rabbits that were rinsed with phosphate-buffered saline to remove blood and aqueous humor before extraction did not yield lesions at any of 200 sites in the recipient animals. The results of this study indicate that retention of T. pallidum infectivity is poor under typical corneal storage conditions and that rabbit corneal tissue contains few, if any, infectious T. pallidum organisms under the experimental conditions employed.

Clinical pathologic correlation of superficial corneal opacities in X-linked ichthyosis.

X-linked ichthyosis is a relatively common oculodermal disorder. Characteristic corneal opacities are small punctate or filiform lesions and are located in the deep corneal stroma. In an unusual case, a 73-year-old man with X-linked ichthyosis and steroid sulfatase deficiency had superficial corneal opacities. The corneal opacities were granular in nature, involving the subepithelial and anterior stromal layers. The opacities resulted in irregular overlying corneal epithelium and were white-gray in color in direct illumination. Histopathologic and electron microscopic studies demonstrated abnormalities of the corneal epithelial basement membrane. The epithelial basement membrane was thickened with irregular extensions into Bowman's layers. Abnormal depositions of basement membrane protein were seen in the anterior stroma. These abnormalities may have resulted from increased production of basement membrane proteins by the corneal epithelium, resulting from hyperactive turnover of the basal layer.

Tetanus prophylaxis following ocular injuries.

The administration of prophylaxis against tetanus following a corneal abrasion is routinely performed in many acute care facilities, despite a lack of support in the literature for its necessity. The risk of developing clinical tetanus from three different types of injuries to the eye was evaluated in an animal model. Clinical tetanus was induced in unimmunized mice by injecting Clostridium tetani organisms or toxin into the anterior chamber. Immunized mice injected intracamerally did not develop signs of tetanus. Tetanus was not induced by topical inoculation of either live organisms or toxin following corneal epithelial debridement or stromal scarification of unimmunized and immunized mice. The results of this study support the administration of prophylaxis against tetanus following perforating ocular injuries. However, our results do not support its routine use following uncomplicated corneal abrasions or other types of nonperforating ocular injuries.