Ectopic pro-opiolipomelanocortin: sequence of cDNA coding for beta-melanocyte-stimulating hormone and beta-endorphin.

A recombinant bacterial plasmid, pMS1, was constructed that contains 318 nucleotides complementary to a portion of pro-opiolipomelanocortin (proOLMC) messenger RNA from an ectopic adrenocorticotropin-producing tumor. The cloned complementary DNA insert, which contains the sequence that codes for all of the beta-melanocyte-stimulating hormone and beta-endorphin portions of proOLMC, as well as the 3' nontranslated section, is identical to the genomic sequence. Hybridization of tumor proOLMC complementary DNA to RNA subjected to electrophoresis and transferred to a nitrocellulose filter revealed two proOLMC messenger RNA species in the tumor polyadenylated RNA, but only one in pituitary polyadenylated RNA. At least one of the tumor proOLMC messenger RNA's is similar, if not identical, to human pituitary proOLMC messenger RNA.

Correlation of fibrosis and transforming growth factor-beta type 2 levels in the eye.

Approximately 1 out of every 10 eyes undergoing surgery for retinal detachment develops excessive intraocular fibrosis that can lead to traction retinal detachment and ultimate blindness. This disease process has been termed proliferative vitreoretinopathy (PVR). The ability to monitor and grade this fibrotic response accurately within the eye as well as the ability to aspirate vitreous cavity fluid bathing the fibrotic tissue makes this an ideal setting in which to investigate the development of fibrosis. Although laboratory studies have recently shown that transforming growth factor-beta (TGF-beta) can enhance fibrosis, little clinical evidence is yet available correlating the level of this or other growth factors with the degree of fibrosis in a clinical setting. We have found that vitreous aspirates from eyes with intraocular fibrosis associated with PVR have more than three times the amount of TGF-beta (1,200 +/- 300 pM [SEM]) found in eyes with uncomplicated retinal detachments without intraocular fibrosis (360 +/- 91 pM [SEM]). Using an in vitro assay, 84-100% of the TGF-beta activity could be blocked with specific antibodies against TGF-beta 2, whereas only 10-21% could be blocked by specific antibodies against TGF-beta 1. TGF-beta 1 was used in an animal model of traction retinal detachment. Since beta 1 and beta 2 have essentially identical biologic effects and only human beta 1 was available in quantities required, beta 1 was chosen for these in vivo studies. The injection of TGF-beta1 plus fibronectin (FN) but not TGF-beta1 alone into the vitreous cavity of rabbits resulted in the increased formation of intraocular fibrosis and traction retinal detachments as compared to control eyes. In previous studies, intravitreal FN levels were also found to be elevated in eyes with intraocular fibrosis.

Systemic amiloride inhibits experimentally induced neovascularization.

Amiloride is an inhibitor of urokinase-type plasminogen activator, and might therefore have an inhibitory effect on neovascularization. Neovascularization was induced in rabbit corneas via local implantation of prostaglandin E1 pellets prepared in a slow-release polymer. Animals received daily intraperitoneal injections of 30 mg of amiloride, or an equivalent volume of saline solution for 5 days; both were well tolerated without severe untoward effect. Neovascular response, as documented by corneal photographs, was evaluated after 5 days of injections. The area of induced corneal neovascularization was decreased by 55% in animals receiving amiloride when compared with controls. Thus, amiloride and similar compounds may prove useful in the study and management of neovascularization.

Visual outcomes following lensectomy and vitrectomy for combined anterior and posterior persistent hyperplastic primary vitreous.

OBJECTIVE: To determine the visual outcome after surgery for persistent hyperplastic primary vitreous using modern vitreoretinal techniques. DESIGN: Retrospective medical record review during a 5-year period (June 1992 to June 1997). Information recorded for each patient included age, medical history, sex, results of preoperative ocular examination, age at diagnosis, procedure performed, intraoperative and postoperative complications, location and number of sclerotomy sites, type of aphakic rehabilitation, amblyopic therapy given, final visual acuity, and length of follow-up. RESULTS: Fourteen patients who underwent surgical management of combined anterior and posterior persistent hyperplastic primary vitreous were identified. Eleven patients underwent aphakic rehabilitation and aggressive amblyopic therapy consisting of occlusive therapy for several waking hours each day. One additional older patient received aphakic rehabilitation only. Ten eyes (71%) achieved a visual acuity of 20/300 or better, and 8 (57%) obtained a final visual acuity of 20/100 or better. Average length of follow-up was 22 months (range, 4-57 months). Nine patients were fitted with an aphakic soft contact lens, 2 older patients had a posterior chamber intraocular lens placed at the time of vitrectomy, and 1 patient wore aphakic spectacles. CONCLUSIONS: With modern vitreoretinal techniques, aphakic rehabilitation, and aggressive amblyopic therapy, useful vision can be obtained in the majority of patients with combined anterior and posterior persistent hyperplastic primary vitreous.

Transforming growth factor beta. A biologic chorioretinal glue.

Transforming growth factor beta (TGF-beta) stimulates fibrosis. We studied its possible role as a bioactive substance for inducing localized chorioretinal wound healing along the edge of a retinal tear. The TGF-beta was applied to induced retinal tears that were examined histopathologically. One day after surgery, neither control nor TGF-beta-treated eyes developed chorioretinal wound healing. Four days, two weeks, and two months after surgery, the control eyes still had not developed chorioretinal wound healing. In contrast, the edges of the retinal tear treated with TGF-beta were adherent to the underlying Bruch's membrane via localized fibrous tissue without apparent effects elsewhere. These results demonstrate intraocular in vivo bioactivity of TGF-beta and suggest that TGF-beta may have a potential role as an alternative means for inducing a chorioretinal adhesion in the treatment of retinal tears.

Retinal complications after aqueous shunt surgical procedures for glaucoma.

OBJECTIVES: To assess retinal complications and to identify risk factors for retinal complications following aqueous shunt procedures. MATERIALS AND METHODS: Records of 38 consecutive aqueous shunt procedures that were performed on 36 patients at the Eye Institute of the Medical College of Wisconsin, Milwaukee, from June 1993 to March 1995 (minimum follow-up, 6 months) were reviewed. The mean +/- SD follow-up was 11.4 +/- 5.2 months (median, 10.5 months). RESULTS: Twelve patients (32%) had the following retinal complications: 4 serous choroidal effusions (10%) that required drainage, 3 suprachoroidal hemorrhages (8%), 2 vitreous hemorrhages (5%), 1 rhegmatogenous retinal detachment (3%), 1 endophthalmitis (3%), and 1 scleral buckling extrusion (3%). Surgical procedures for retinal complications were required in 8 (67%) of these 12 patients. Visual acuity decreased 2 lines or more in 9 (75%) of these 12 patients. The median onset of a postoperative retinal complication was 12.5 days, with 10 patients (83%) experiencing complications within 35 days. Serous choroidal effusions developed in 10 other patients (26%), and these effusions resolved spontaneously. Visual acuity decreased 2 lines or more in 2 (20%) of these additional 10 patients. Patients who experienced serious retinal complications were significantly older, had a higher rate of hypertension, and postoperative ocular hypotony. Serious retinal complications were distributed evenly among patients with Krupin valves with discs and Molteno and Baerveldt devices. Experience with the Ahmed glaucoma valve implant was limited. CONCLUSION: Aqueous shunt procedures may be associated with significant retinal complications and subsequent visual loss.

Transpupillary thermotherapy of occult choroidal neovascularization in age-related macular degeneration.

PURPOSE: To evaluate the efficacy of transpupillary thermotherapy (TTT) in management of occult subfoveal choroidal neovascularization (CNV) in exudative age-related macular degeneration (AMD). METHODS: Retrospective chart review of eyes that were treated with TTT and had at least 12 weeks of follow-up. Base-line and final ETDRS visual acuity and fluorescein angiography (FA) were compared. RESULTS: For the 48 eyes which met inclusion criteria, mean pre-operative visual acuity was 20/128 (range: 20/50-20/500). Average follow-up was 27 weeks (range: 12 weeks-55 weeks). At 3 months after treatment, 12 eyes (25%) improved 2 lines or more, 18 eyes (37.5%) had no change or 1 line of visual improvement, and 18 eyes (37.5%) worsened 1 or more lines. No significant adverse event was noted during treatment. Three eyes developed large submacular hemorrhage within 2 months of treatment. Based on clinical examination and FA, 61% of the eyes appeared to have reduction of subretinal fluid compared to pre-operative evaluations. CONCLUSION: Visual acuity was stable or improved in 62.5% of eyes in our series and the treatment was well tolerated. Longer follow up and larger number of patients would be required to evaluate the ultimate benefit of TTT in management of occult CNV due to AMD.

The adjustable globe: a technique for adjustable strabismus surgery.

BACKGROUND: Conventional adjustable strabismus surgery involves postoperative repositioning of individual muscles anchored to the sclera via adjustable sutures. Greaves has described anchoring opposing rectus muscles to one another, via sutures passing on either side of the limbus. With the muscles disinserted, the "freed" globe can be adjusted to the desired position within the resulting suture cradle. Friction of the sutures against the sclera holds the muscles in place until healing occurs. METHODS: Using a cul-de-sac approach, we performed 23 horizontal and three vertical adjustable globe procedures, with median follow-up of 7 weeks. Four procedures were performed on nonhuman primates, monitored with iris fluorescein angiography. RESULTS: Esodeviations were well corrected, but exodeviations were often grossly undercorrected. Prolonged postoperative discomfort and photophobia were experienced. Possible evidence for mild anterior segment ischemia was noted. CONCLUSION: Concern about poor results with exodeviations, discomfort, and possible anterior segment ischemia led us to abandon this procedure.

The use of topical aqueous suppressants in the prevention of postoperative intraocular pressure elevation following pars plana vitrectomy with long-acting gas tamponade.

PURPOSE: To determine if topical aqueous suppressant therapy applied after pars plana vitrectomy (PPV) with gas tamponade successfully prevents postoperative elevation of intraocular pressure (IOP). METHODS: A prospective, controlled study was performed on patients who met inclusion criteria and underwent PPV with gas tamponade (SF6 18%-20% or C3F8 12%-16%) over a 1-year period. Treatment eyes received topical aqueous suppressants at the end of surgery. Postoperative IOP checks were performed at 4 to 6 hours, 1 day, and 1 week. RESULTS: Twenty-one control (C) and 20 treatment (T) eyes met the inclusion criteria. The IOP (in mm Hg) measured at 4 to 6 hours (23.05 [C], 14.73 [T] and 1 day (23.24 [C], 17.28 [T]) postoperatively showed a statistically significant difference between the groups (P = .0038) at 4 to 6 hours, and a trend toward significance (P = .057) at 1 day. Eleven control and 3 treatment eyes had an IOP spike above 25 mm Hg at 4 to 6 hours or 1 day postoperatively (P = .02), and 6 control and 1 treatment eye had a postoperative IOP above 30 mm Hg. A pressure rise above 40 mm Hg was seen in 2 control eyes and no treatment eyes. CONCLUSIONS: Use of topical aqueous suppressants following PPV with long-acting gas tamponade is effective in preventing significant postoperative IOP elevation in a majority of cases.