Bilateral diffuse uveal melanocytic proliferation associated with extraocular cancers: review of a process particularly associated with gynecologic cancers.

We reviewed cases of a paraneoplastic syndrome in which uveal melanocytes proliferated and led to blindness. Eighteen cases were derived from the literature, and two were taken from our institution. The average patient age at the time of the diagnosis was 63 years (range, 34-89 years). There were 13 women and 7 men. In approximately half of the cases, the ocular symptoms antedated those of the inciting tumor. Most of the inciting tumors were poorly differentiated carcinomas. The most common tumors were from the female genital tract (ovary and uterus) among the women patients and from the lung among the men. Tumors from the breast were rare (one possible case), and tumors of the prostate were conspicuously absent. All five inciting tumors whose histopathology was reviewed expressed neuron-specific enolase, but none prominently expressed antigens more specific for neuroendocrine carcinomas such as chromogranin or synaptophysin. It is our experience that many general pathologists are not aware of this unique paraneoplastic syndrome. Our report is the first to document a statistically significant association between this syndrome and gynecologic cancers.

Complications of surgery for subfoveal choroidal neovascularization.

Advancing surgical techniques have made the surgical excision of subfoveal CNV possible in all cases. However, serious surgical complications lead to a limited visual outcome in many cases. The major complications that cause poor visual outcome are related to poor case selection and include injury to the RPE, with secondary atrophy of the choriocapillaris and damage to the neurosensory retina, and a high rate of persistent or recurrent CNV. Patients with POHS have localized disease of the RPE-Bruch's membrane complex and typically have CNV growing between the RPE and neurosensory retina (type 2 CNV). These patients have the best visual prognosis postoperatively because of the potential for maintaining native RPE beneath the fovea. Patients with AMD typically have CNV growing beneath the RPE (type I CNV). These patients are poor surgical candidates because the surgical excision of type I CNV is almost always associated with débridement of native subfoveal RPE and a poor visual outcome. Presently, all surgical studies have been retrospective and are characterized by limited follow-up. Therefore, whether surgical excision of subfoveal CNV is beneficial as compared to mere observation is uncertain. A large, randomized, prospective study currently is being performed. These Submacular Surgery Trials will attempt to determine whether these surgical procedures are more efficacious than observation and whether the benefits outweight the risks of surgery in these patients.

Photodynamic biologic tissue glue in perforating rabbit corneal wounds.

OBJECTIVE: To evaluate the in vivo wound modulating effects of a new biologic tissue adhesive. BACKGROUND DATA: Biological tissue glue can serve as an important adjunct technology in the treatment of a number of ocular conditions, including closure of corneal wounds. These experiments were performed to evaluate the wound healing effects of a new photodynamic biologic tissue glue (PBTG) in perforating rabbit corneal incisions. METHODS: Perforating corneal wounds were created in 12 pigmented rabbits. Two perforating incisions were made 180 degrees apart 2 mm from the limbus. One incision in each eye was closed with a single interrupted 10-0 nylon suture, and the other closed with PBTG. Rabbits were followed biomicroscopically and sacrificed at 1-, 3-, and 7-week intervals for histological evaluation of their corneal wounds. RESULTS: There were no clinical signs of PBTG-related toxicity in any of the rabbits. Compared to control wounds, all glued corneas had greater epithelial filling, less stromal edema, and fewer inflammatory cells at the 1-, 3-, and 7-week stages and showed greater overall wound maturation. CONCLUSION: Our data suggest that PBTG is an effective and nontoxic tissue adhesive that accelerates normal corneal wound healing.

Photodynamic tissue adhesion with chlorin(e6) protein conjugates.

PURPOSE: To test the hypothesis that a photodynamic laser-activated tissue solder would perform better in sealing scleral incisions when the photosensitizer was covalently linked to the protein than when it was noncovalently mixed. METHODS: Conjugates and mixtures were prepared between the photosensitizer chlorin(e6) and various proteins (albumin, fibrinogen, and gelatin) in different ratios and used to weld penetrating scleral incisions made in human cadaveric eyes. A blue-green (488-514 nm) argon laser activated the adhesive, and the strength of the closure was measured by increasing the intraocular pressure until the wound showed leakage. RESULTS: Both covalent conjugates and noncovalent mixtures showed a light dose-dependent increase in leaking pressure. A preparation of albumin chlorin(e6) conjugate with additional albumin added (2.5 protein to chlorin(e6) molar ratio) showed significantly higher weld strength than other protein conjugates and mixtures. CONCLUSIONS: This is the first report of dye-protein conjugates as tissue solders. These conjugates may have applications in ophthalmology.

Practice patterns in diabetic retinopathy: part 1: analysis of retinopathy follow-up.

OBJECTIVE: To evaluate ophthalmologists' management of diabetic patients. METHODS: A multiple-choice questionnaire was mailed to all ophthalmologists in New York (1985), Florida (1990), and Massachusetts (1993 and 1996). Questions included practice patterns, methods used in examination, use of photography and fluorescein angiography, indications for laser treatment, and intervals for follow-up of selected conditions. Responses were tabulated and compared between surveys and with the American Academy of Ophthalmology Preferred Practice Pattern. RESULTS: In this first report, we detail follow-up patterns of various grades of retinopathy. Physicians increasingly used duration of diabetes as a criterion in determining the length of follow-up for adults, despite persistent ambiguities for children. There were notable changes over time in nearly all aspects of follow-up for both general ophthalmologists and retina specialists. Retina specialists were less likely to treat proliferative disease, more likely to follow up patients with preproliferative disease sooner, and used longer follow-up intervals for short-duration diabetic patients, whereas a small percentage of general ophthalmologists continued to recommend treatment for background disease. CONCLUSION: There were noticeable trends toward Diabetes 2000 recommendations over time, although there remained many areas where further education appeared warranted.

Relative strength of photodynamic biologic tissue glue in penetrating keratoplasty in cadaver eyes.

PURPOSE: To compare the relative strength of photodynamic biologic tissue glue (PBTG) with that of 10-0 nylon sutures in closing penetrating keratoplasty (PKP) wounds in cadaver eyes. SETTING: Corneal Research Laboratory, University of Chicago, Chicago, Illinois, USA. METHODS: A 7 mm central corneal trephination was performed on 8 recently enucleated human eyes. Each corneal button was removed and then resutured in its original position, using 4 interrupted 10-0 nylon cardinal sutures and PBTG (n = 7) or 16 interrupted 10-0 nylon sutures (n = 1). Wound leak and incisional bursting pressures were determined. RESULTS: The average pressure at which wound leak and iris prolapse occurred was 124 mm Hg (range 70 to 180) and 185 mm Hg (range 90 to 300), respectively. The pressure required to create wound leak increased as the time between glue application and pressurization of the globe lengthened (mean 22 minutes, range 5 to 60 minutes), indicating that the bonding and stability of the adhesive increased with time. In contrast, the control eye developed wound leak at 70 mm Hg and iris prolapse at 300 mm Hg. CONCLUSIONS: Photodynamic biologic tissue glue was comparable to sutures in providing adequate corneal wound strength in PKP in a cadaver eye model. Wound closure with PBTG may reduce the number of sutures required in corneal transplantation and decrease the incidence of suture-related complications and allograft rejection.

Melanocytomas of the optic nerve and uvea.

Melanocytomas are an example of changing attitudes toward clinical management of intraocular tumors. They also might exemplify the power of pathological examination and follow-up in patient care and treatment. Prior to the observations of Zimmerman [10], most patients with melanocytomas underwent enucleation. Today, these patients are followed up conservatively and continue to enjoy vision. Melanocytomas are fairly uncommon tumors found more often in blacks and hyperpigmented individuals than in whites. Women are slightly more likely to have this tumor than are men. Melanocytomas are uniformly densely hyperpigmented lesions found on the optic nerve, choroid, ciliary body, and iris and are benign, stationary tumors that seldom cause symptoms or secondary complications. In patients with papillary melanocytomas, the most common visual disturbance is enlargement of the blind spot. With larger tumors, an afferent pupillary defect may be noted. Ciliary body and iris tumors may cause secondary anterior segment complications such as glaucoma, hyphema, or ectopia. Dispersion of pigment by melanocytomas is common and should not necessarily be interpreted as a sign of malignant transformation. Ancillary tests such as fluorescein angiography, ICG angiography, ultrasonography, CT, MRI, and the 32P test are of little clinical benefit in differentiating between melanocytomas and malignant melanomas and may lead to erroneous conclusions. Treatment for melanocytomas is conservative, its mainstay being serial clinical examinations, fundus photography, and visual field examinations to record tumor size and document growth. Lesions that grow rapidly may have transformed to a malignant melanoma and should be treated accordingly.

Photodynamic biologic tissue glue to enhance corneal wound healing after radial keratotomy.

PURPOSE: To evaluate the effect of photodynamic biologic tissue glue (PBTG) on corneal wound healing after radial keratotomy (RK). SETTING: Cornea Research Laboratory, The University of Chicago, Chicago, Illinois, USA. METHODS: Bidirectional, eight-incision RK was done in one eye of eight Dutch pigmented rabbits. Then, PBTG was inserted into the RK incisions and activated with an argon blue-green laser in four treatment eyes. The rabbits were divided into three groups: early, in which corneal wound healing was assessed at 1 and 3 weeks; late, in which corneal wound healing was assessed at 8 weeks; enhancement. RESULTS: The PBTG-treated keratotomy wounds had a more prominent epithelial healing response immediately after RK and a decreased propensity for wound dehiscence. Collagen fiber arrangement in the PBTG-treated incisions was sagittal to the keratotomy wound 1 to 3 weeks after RK and then changed to a transverse orientation across the keratotomy wound by 8 weeks. The control keratotomy wounds had a less prominent epithelial healing response and developed late disorganization of the posterior keratotomy wound at 8 weeks. Keratometry measurements 2 months after RK showed corneal flattening of 1.0 diopter (D) in the PBTG-treated eye and 6.5 D in the control eye, which is consistent with histologic studies showing more advanced wound healing in the PBTG-treated eyes. After RK enhancement, the PBTG-treated eye resisted further corneal flattening and had 4.5 D of corneal steepening; the control eye had 2.0 D of additional corneal flattening. CONCLUSION: The nontoxic, laser-activated adhesive PBTG accelerated corneal wound healing after RK and simulated the placement of sutures into the RK wound. Thus, PBTG may be an alternative to sutures to correct hyperopia after RK in humans.

Practice revenue and cost distribution for ophthalmology, 1988 to 1993.

As opthalmologists need to better manage their practices, information regarding distribution of practice costs becomes more relevant. In this study, we compare revenues and costs from published sources to determine changes over time and across surveys. We also evaluate the reliability and validity of these statistics. Data were obtained from the Health Care Financing Administration (for 1988), the American Medical Association (for 1988, 1990, 1992, and 1993), and the Medical Group Management Association (for 1988, 1990, 1992, and 1993) and were compared across years and surveys. We found large differences among the surveys in both dollar amounts and percentages of total revenue for some of the reported cost categories. Analysis of the data over time showed less of a decline in physician earnings than expected, although there were large increases in the category "other costs." We found considerable divergence among the statistical results. Opthalmologists, public policymakers, and managed care organizations must exercise great caution in interpreting such data and in applying their findings to individual ophthalmic practices and practitioners.

Photodynamic biologic tissue glue.

We studied both heat- and light-activated tissue glues, and while a heat-activated mixture such as albumin and fluorescein isothiocyanate was effective, we believed that a light-activated substance would have less of an effect on adjacent tissue. Our glue uses a photosensitive singlet oxygen generator to cross-link a protein solder with corneal stromal collagen. The mixture consists of 18% fibrinogen and 2.6 mg/ml of riboflavin-5-phosphate activated with a blue-green (488-514 nm) Argon laser. We tested our glue by soldering 5-mm penetrating central corneal incisions made in human cadaver eyes. The strength of the closure was measured by cannulating the vitreous cavity with an 18-gauge needle connected to a saline reservoir. The pressure in the reservoir was elevated by connecting it to a sphygmomanometer. Immediately following tissue closure, the intraocular pressure was increased until the wound burst. We soldered and measured 10 eyes and found a mean bursting pressure of 154 mm Hg, with a range of 80-260 mm Hg. Our laser-activated tissue glue is an effective adhesive for corneal tissue, and we now plan to carry out toxicity studies in living animals.