Pars plana vitrectomy, subretinal injection of tissue plasminogen activator, and fluid-gas exchange for displacement of thick submacular hemorrhage in age-related macular degeneration.

PURPOSE: To evaluate a new procedure for displacement of large, thick submacular hemorrhage in patients with age-related macular degeneration. METHODS: Retrospective review of 11 eyes of 11 patients with age-related macular degeneration and thick submacular hemorrhage (defined as causing retinal elevation detectable on stereo fundus photographs) treated with vitrectomy, subretinal injection of tissue plasminogen activator (25 or 50 microg), and fluid-gas exchange with postoperative prone positioning. Outcome measures included displacement of hemorrhage from the fovea, best postoperative visual acuity, and final postoperative visual acuity. RESULTS: In the 11 affected eyes of 11 patients (seven men and four women; mean age, 76 years), preoperative visual acuity ranged from 20/200 to hand motions. With surgery, subretinal hemorrhage was displaced from the fovea in all 11 cases. Mean postoperative follow-up was 6.5 months (range, 1 to 15 months). Best postoperative visual acuity varied from 20/30 to 5/200, with improvement in nine (82%) cases and no change in two cases. Eight eyes (73%) measured 20/200 or better, with four of these eyes (36%) 20/80 or better. Final postoperative visual acuity ranged from 20/70 to light perception, with improvement in eight (73%) cases, no change in one case, and worsening in two cases. A statistically significant difference was found between preoperative and best postoperative visual acuity (P =.004) but not between preoperative and final visual acuity (P =.16). Hemorrhage recurred in three (27%) eyes, causing severe visual loss in one eye. CONCLUSIONS: This technique displaces submacular hemorrhage from the fovea and can improve vision in patients with age-related macular degeneration. However, recurrence of hemorrhage occurred in 27% of eyes and caused severe visual loss in one eye. A randomized, prospective clinical trial is necessary to determine the efficacy of this technique in comparison with other proposed treatments.

Management of eyes with both idiopathic macular hole and choroidal neovascularization.

PURPOSE: To describe the characteristics, treatment, and outcome of five eyes with both choroidal neovascularization (CNV) and macular hole. METHODS: Medical records of five patients with both macular hole and CNV were reviewed. RESULTS: All eyes had full-thickness macular holes. Most eyes had atypical-appearing macular holes (subretinal hemorrhage, prominent subretinal fluid, or discoloration at the hole margin) at presentation or subsequently when CNV developed. Fluorescein angiography (FA) confirmed the presence of CNV in each eye. Three eyes underwent combined macular hole repair and CNV removal, and sustained closure of these macular holes was achieved. A fourth eye underwent successful argon laser photocoagulation of extrafoveal CNV, and macular hole surgery was declined. The final eye underwent two macular hole repairs before sustained closure was achieved. Final visual acuity, ranging from 20/100 to hand motions, was limited by macular pathology and/or cataract. CONCLUSIONS: Choroidal neovascularization can occur in association with a macular hole. In eyes with an atypical-appearing macular hole, FA should be obtained to detect CNV. Excision of the CNV can be done safely in conjunction with macular hole surgery. Final visual acuity may be limited by cumulative retinal and retinal pigment epithelium damage, especially in eyes with underlying macular disease.

Fluocinolone acetonide sustained drug delivery device to treat severe uveitis.

PURPOSE: Uveitis is often a chronic disease requiring long-term medical therapy. In this report, we describe a pilot safety and efficacy trial of a novel sustained drug delivery system containing fluocinolone acetonide to treat patients with severe uveitis. DESIGN: Prospective, noncomparative, interventional case series PARTICIPANTS: Patients with severe uveitis. METHODS: Sustained drug delivery devices designed to release fluocinolone acetonide for at least 2.5 years were implanted through the pars plana into the vitreous cavity of seven eyes of five patients. All patients had severe uveitis not well controlled with, or intolerant to, repeated periocular corticosteroid injections, systemic corticosteroids, nonsteroidal immunosuppressive agents, or a combination thereof at the time of device implantation. Before device implantation, patients underwent complete evaluation including history, ophthalmologic examination, fluorescein angiography, visual field testing, and electroretinography. After surgery, patients were reexamined at 1 week, 2 weeks, 4 weeks, and at 1- to 3-month intervals. Visual fields, electroretinograms, and fluorescein angiography were repeated at 3- to 6-month intervals. MAIN OUTCOME MEASURES: Preoperative and postoperative visual acuity, ocular inflammation, anti-inflammatory medication use, and intraocular pressure. RESULTS: Patients had a diagnosis of Behçet's syndrome (two eyes), or idiopathic panuveitis (five eyes, including two with necrotizing retinitis, two with progressive chorioretinitis, and one with iridocyclitis and intermediate uveitis). Patients were observed an average of 10 months (range, 5-19 months). All eyes had stabilized or improved visual acuity after device implantation, and four of seven eyes had an improvement of three lines or more. The mean initial visual acuity, measured by Snellen chart, was 20/207, and the mean final visual acuity was 20/57 (P = 0.02). After surgery, at the final visit, no eye had clinically detectable inflammation, and all seven eyes had a marked reduction in systemic, topical, and periocular anti-inflammatory medication use. Four eyes had increased intraocular pressure 6 weeks to 6 months after device implantation. Intraocular pressure has been controlled on topical medications. No patient experienced intraoperative complications. CONCLUSIONS: A fluocinolone acetonide sustained drug delivery device is a promising new therapy for the treatment of severe uveitis. Intraocular pressure must be carefully monitored long after device implantation. Based on these data, a randomized study of a larger group of patients is warranted.

Pharmacokinetics of the fluocinolone/5-fluorouracil codrug in the gas-filled eye.

PURPOSE: To determine the effect of intraocular gas tamponade on drug levels achieved with the intravitreal sustained-release fluocinolone (FL)/5-fluorouracil (5-FU) codrug pellet. METHODS: After insertion of a 10-mg codrug pellet into the right eyes of 43 New Zealand white rabbits, perfluoropropane (0.4 mL of 100% C3F8) or a control sham was then injected into the midvitreous cavity. On postoperative days 2, 4, 7, 21, and 42, aqueous samples were collected, the rabbits were killed, and the right eyes were enucleated. The vitreous and remaining codrug pellet were then isolated. Pellet and intravitreal drug levels were determined by high-pressure liquid chromatography. RESULTS: No measurable drug levels were detected in any of the aqueous samples. Maximal gas expansion occurred by day 4 and partial resorption was observed by days 14 to 21. Vitreous FL and 5-FU levels during C3F8 expansion (day 2) were statistically significantly higher in the gas-filled eyes. On postoperative days 4, 7, 21, and 42, there were no statistically significant differences between FL and 5-FU drug levels in eyes containing C3F8 as compared with control eyes. Pellet codrug, FL, and 5-FU levels over time were similar in gas-filled and control eyes. CONCLUSIONS: Intraocular gas tamponade does not significantly affect the sustained intravitreal drug levels achieved with the FL/5-FU codrug. If clinically efficacious, the FL/5-FU codrug formulation does not need to be altered to treat proliferative vitreoretinopathy in the presence of intraocular gas.

Diagnosis of vitreoretinal adhesions in macular disease with optical coherence tomography.

PURPOSE: To compare the relative incidence of vitreoretinal adhesions associated with partial vitreous separation within the macula diagnosed with optical coherence tomography (OCT) with that of those diagnosed with biomicroscopy. METHODS: The authors obtained linear cross-sectional retinal images using OCT in patients with selected macular diseases. Additional studies included biomicroscopy, fundus photography, fluorescein angiography, and B-scan ultrasonography. RESULTS: Optical coherence tomography was performed on 132 eyes of 119 patients. Vitreoretinal adhesions within the macula were identified using OCT in 39 eyes (30%) with the following diagnoses: idiopathic epiretinal membrane (n = 13), diabetic retinopathy (n = 7), idiopathic macular hole (n = 7), cystoid macular edema (n = 7), and vitreomacular traction syndrome (n = 5). Biomicroscopy identified vitreoretinal adhesions in only 11 eyes (8%). Two distinct vitreoretinal adhesion patterns were identified with OCT, each associated with partial separation of the posterior hyaloid face: focal (n = 25) and multifocal (n = 14). CONCLUSIONS: Optical coherence tomography is more sensitive than biomicroscopy in identifying vitreoretinal adhesions associated with macular disease.

Vitrectomy update for macular traction in ocular toxocariasis.

PURPOSE: To study the results of modern vitrectomy in traction and combined traction-rhegmatogenous retinal detachment involving the macula in cases of ocular toxocariasis. METHODS: This was a cohort study of patients seen in different institutions in the United States. Ten eyes of 10 patients were studied. Vitrectomy was performed in all eyes, combined with membrane removal, scleral buckle, fluid-gas exchange, silicone oil, or lensectomy in certain cases. The anatomic and visual results of surgery were reviewed. RESULTS: Ten eyes from 10 patients ranging in age from 2 to 33 years (median, 6 years) were reviewed. Follow-up ranged from 3 months to 8 years (median, 2 years). All eyes achieved macular attachment following surgery; vision improved in 5 (50%) eyes, and was unchanged in 5 (50%). Histologic specimens from six eyes were reviewed, and revealed combinations of fibrous tissue, eosinophils, plasma cells, lymphocytes, and giant cells. One specimen revealed an encysted Toxocara canis organism. CONCLUSION: Inflammation created in response to Toxocara larvae may lead to traction retinal detachment of the macula. Vitreoretinal surgery has a good chance of reattaching the macula and improving vision.

Long-term effect on the equine eye of an intravitreal device used for sustained release of cyclosporine A.

OBJECTIVE: To determine the long-term toxicity of an intravitreal device releasing continuous cyclosporinee A (CsA) in normal eyes of horses by evaluating clinical signs, electroretinography, and histopathology. Animals Studied Ten adult horses with normal ophthalmic examinations were used in this study Procedure(s) Four horses had one eye implanted with a CsA device, and six horses had the right eye implanted with a CsA-containing device (10 eyes with CsA in total) and the left eye (six eyes in total) with the device without drug (control). The implants were placed in the vitreous of the eyes through a sclerotomy 1 cm posterior to the limbus in the dorso-temporal quadrant of the eye. Scotopic electroretinograms were performed prior to implantation and at 1 week, and at 1, 3, 6, 9, and 12 months postimplantation. Two of the unilaterally implanted horses were euthanized at 1 weeks postimplantation, and two at 6 weeks postimplantation. Two of the bilaterally implanted horses were euthanized at 6 months, two at 9 months, and two at 12 months postimplantation. At euthanasia, the eyes were removed, aqueous and vitreous humor aspirated, and tissues fixed in 10% buffered formalin and processed for histopathology. CsA concentrations were measured by high pressure liquid chromatography in the aqueous and vitreous humors, and in peripheral blood. RESULTS: The devices were tolerated well in 14 of 16 eyes. There was minimal postoperative inflammation in most eyes, with a normal appearance within 7 days. In two eyes implanted with the CsA device, severe inflammation resulted in phthisis bulbi by 28 days. One of these eyes exhibited suspected bacterial endophthalmitis, and one had a sterile endophthalmitis and cataract presumably from trauma to the lens during implantation. In the other 14 eyes, no change was observed in the scotopic electroretinograms (ERG) from preoperative results, and no significant differences between the right (CsA) and left (control device) eyes were observed. CsA levels in the aqueous and vitreous humor, and peripheral blood were below the detection limit of the HPLC. Histologic findings revealed only a mild lymphoplasmacytic cellular infiltrate in the ciliary body and pars plana near the implantation site. CONCLUSIONS: The CsA devices were well tolerated with no long-term complications from the implants themselves. However, complications may occur from inadvertent implantation trauma or contamination during surgery. The long-term safety of the device may make it useful for delivery of CsA in the control of equine recurrent uveitis.

The importance of fluorescein angiography in planning laser treatment of diabetic macular edema.

OBJECTIVE: To test the hypothesis that pretreatment fluorescein angiography (FA) is not necessary for effective laser treatment of patients with clinically significant diabetic macular edema (CSME). DESIGN: Prospective, randomized, controlled treatment simulation. PARTICIPANTS: Six fellowship trained retina specialists. INTERVENTION: The authors compared the ability of four retina specialists (observers) to plan laser treatment with and without the use of FA. One hundred consecutive cases of CSME were selected, each case consisting of a stereo pair of color photographs and a corresponding fluorescein angiogram. These cases were first read by two retina specialists who reached consensus on a treatment plan for each case (standard map). Each of the 4 observers reviewed 50 of these cases on 2 occasions and plotted 2 sets of treatment maps, 1 set created with and 1 without the aid of FA. Each observer's 100 treatment maps were graded for accuracy by comparing them to the corresponding standard maps. The role of FA in improving the accuracy of treatment maps was evaluated using logistic regression analysis to control for different observers, different cases, and different posterior pole characteristics. MAIN OUTCOME MEASURES: Accuracy was defined as the proportion of standard treatment correctly treated by the observer. RESULTS: For the observers as a group, the use of FA improved treatment planning accuracy from 49% to 54.5% (P = 0.02); however, there was significant interobserver variation in performance (P < 0.001). Treatment planning accuracy without and with FA was as follows: observer 1, 40.8% and 40.2%; observer 2, 49.8% and 72%; observer 3, 56.1% and 59.5%; and observer 4, 49.2% and 46.4%. CONCLUSION: The use of FA improves the accuracy of treatment planning for CSME. The authors' study supports the use of FA in laser treatment of patients with CSME.

Suppression of NF-kappaB-dependent proinflammatory gene expression in human RPE cells by a proteasome inhibitor.

PURPOSE: To determine whether nuclear transcription factor-kappaB (NF-kappaB) is activated in human retinal pigment epithelial (hRPE) cells in response to interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), or interferon-gamma (IFN-gamma) alone or in combination and if so, whether expression of proinflammatory genes induced by these agents can be blocked by a proteasome inhibitor, MG-132, which inhibits the degradation of I kappaB, an NF-kappaB inhibitor, thereby preventing nuclear translocation of NF-kappaB. METHODS: Cultured hRPE were pretreated for 60 minutes with medium alone or medium containing the proteasome inhibitor MG-132 (20 microM) and then exposed to TNF-alpha (1.1 x 10(3) U/ml), IL-1beta (5 U/ml), or IFN-gamma (7.5 x 10(3) U/ml) alone or in combination (TII). Nuclear translocation of NF-kappaB was determined by fluorescence staining of the NF-kappaB Rel A (p65) subunit. Cytoplasmic I kappaB protein was measured by western blot analysis. Nuclear extract binding to kappaB DNA motifs was measured by electrophoretic mobility shift assay and antibody supershift assay. Steady state mRNA expression of the chemokines melanoma growth stimulating activity (MGSA)/gro-alpha, regulated on activation normal T-cell expression and secreted (RANTES), and monocyte chemoattractant protein (MCP-1), the cytokines IL-1beta and macrophage colony stimulating factor (M-CSF) and intercellular adhesion molecule-1 (ICAM-1) was evaluated by semiquantitative reverse transcription-polymerase chain reaction. Chemokine and cytokine protein secretion was measured by enzyme-linked immunosorbent assay. Cell-surface ICAM-1 expression was determined by flow cytometry. RESULTS: TNF-alpha, IL-1beta, and TII but not IFN-gamma alone caused degradation of I kappaB, Rel A nuclear translocation, and increased NF-kappaB DNA binding activity, effects that were blocked by pretreatment with MG-132. MG-132 suppressed MGSA/gro-alpha, RANTES, MCP-1, IL-1beta, M-CSF, and ICAM-1 mRNA expression and secreted RANTES, MCP-1, and M-CSF protein, and cell-surface ICAM-1 that were induced by IL-1beta, TNF-alpha, and TII. CONCLUSIONS: TNF-alpha, IL-1beta, and TII induce expression of proinflammatory cytokines and ICAM-1 in hRPE cells through an NF-kappaB-dependent signal transduction pathway. This effect is blocked by MG-132, a proteasome inhibitor that prevents I kappaB degradation. Inhibition of NF-kappaB may be a useful strategy to treat proliferative vitreoretinopathy and uveitis, ocular diseases initiated and perpetuated by cytokine activation.

Methotrexate treatment for sarcoid-associated panuveitis.

OBJECTIVE: To determine the safety and efficacy of low-dose methotrexate (MTX) for sarcoid-associated panuveitis. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Twenty eyes from 11 patients were analyzed. Eight patients had sarcoidosis. Three patients were clinically suspected of sarcoidosis despite negative laboratory testing. All charts of patients with sarcoidosis and idiopathic uveitis seen by the Duke Uveitis Service from 1989 to 1997 were retrospectively reviewed. Those with sarcoid-associated or sarcoid-suspected panuveitis treated with MTX with a minimum of 6 months of follow-up were studied. INTERVENTION: Low-dose MTX was administered to patients weekly and patients were followed with serial ophthalmologic and medical examinations. MAIN OUTCOME MEASURES: Visual acuity, oral and topical corticosteroid requirements, anterior chamber inflammation, and ability to undergo successful cataract extraction were used to measure the efficacy of MTX therapy. RESULTS: After MTX treatment was initiated, 90% of eyes had preserved or improved visual acuity. Mean initial Snellen visual acuity was 20/62 and mean final acuity was 20/40 (P = 0.044). Of those patients initially requiring oral corticosteroids, the dosage was decreased in 100%, and they were completely discontinued in 86%. The mean initial oral corticosteroid dose was 26.6 mg and the mean final dose was 1.5 mg (P = 0.012). Topical corticosteroids were decreased in 63% of eyes. The mean initial use was once every 1.6 hours, and the mean final use was once every 3.9 hours (P = 0.001). Ninety-five percent of eyes had stabilized or decreased inflammation. The mean initial inflammation score was 1.2, and the mean final score was 0.5 (P = 0.007). Five of six eyes previously unable to have cataract extraction because of uncontrolled inflammation became quiet on MTX and underwent surgery. One hundred percent of these eyes had improved vision after surgery. Side effects were mild and transient or reversible. CONCLUSION: Low-dose MTX is an effective and safe adjunct to treat chronic sarcoid-associated panuveitis.

Management of complications in eyes containing two intraocular lenses.

OBJECTIVE: To describe the management of complications in eyes containing two intraocular lenses (IOLs). DESIGN: A retrospective noncomparative case series. PARTICIPANTS: Eight patients having a dislocated posterior chamber intraocular lens (PC IOL) and a secondary anterior chamber intraocular lens (AC IOL) participated. INTERVENTION: Surgical treatment of complications, including mobile dislocated PC IOLs in five eyes and retinal detachment in three eyes, was performed. MAIN OUTCOME MEASURES: Visual acuity and anatomic status were evaluated. RESULTS: Dislocated PC IOLs were removed through a pars plana incision in five eyes and a limbal incision in three eyes. Retinal detachments were repaired in three eyes. With follow-up from 7 months to 6.5 years, visual acuities ranged from 20/25 to 20/40 in five eyes and 20/60 to 20/400 in the three eyes undergoing retinal detachment repair. CONCLUSION: Eyes in which dislocation of a PC IOL occurs during or after cataract surgery may have significant complications develop. Successful surgical repair is more complex in the presence of a secondary AC IOL.

Intraocular lens changes after short- and long-term exposure to intraocular silicone oil. An in vivo study.

OBJECTIVE: Silicone oil frequently is used as a vitreous substitute after complex vitreoretinal procedures. The authors sought to study the effect of short- and long-term exposure to silicone oil on polymethyl methacrylate (PMMA, MC60BM; Alcon, Ft. Worth, TX), silicone (SI-30NB; AMO, Irvine, CA), and soft acrylic (MA60BM; Alcon) intraocular lenses (IOLs). DESIGN: An experimental animal study. INTERVENTION: Forty-one New Zealand white rabbits underwent lensectomy, vitrectomy, capsulotomy, and placement of one of the three types of IOLs into the ciliary sulcus. All lenses were weighed before implantation and 24 hours after explanation. In the short-term study, an fluid-air exchange was performed followed by the use of silicone oil (1000 centistokes) to coat the posterior lens surface. Immediately thereafter, an air-fluid exchange was performed and the remaining silicone on the posterior lens surface was aspirated or wiped or both for 1 minute using a soft-tipped extrusion cannula for 1 minute. In the long-term study, the posterior segment was filled with 1000 centistokes silicone oil after fluid-air exchange. Animals were observed by slit-lamp biomicroscopy and photographed at 1 week, 1 month, and 3 months after surgery. At 3 months, all animals underwent silicone-fluid exchange, an attempt to manually remove any remaining silicone oil, and lens explanation. RESULTS: In the short-term study, no silicone oil remained after manual wiping and/or aspiration in any of the four rabbits implanted with PMMA or acrylic IOLs. In the animals with silicone IOLs, a significant amount of silicone oil remained on the posterior lens surface of all lenses (P < 0.01 for silicone vs. acrylic and silicone vs. PMMA). No statistically significant difference was found when comparing the lens weights in each group before and after implantation. In the long-term study, aqueous droplet formation was found on the posterior lens surface of six of nine PMMA IOLs and ten of ten silicone IOLs at 3 months. No opacities were observed in the group with acrylic IOLs (P < 0.001 for acrylic vs. silicone, P = 0.0018 for acrylic vs. PMMA, and P = 0.047 for PMMA vs. silicone). Adherent silicone oil remained on two of nine PMMA IOLs and on none of ten acrylic IOLs. In contrast, a significant amount of silicone oil remained on the posterior lens surface of ten of ten silicone IOLs (P < 0.001 for silicone vs. acrylic and silicone vs. PMMA). Furthermore, there was a statistically significant increase in lens weights before and after implantation in the silicone IOL group but not in the PMMA or acrylic group (P < 0.01). CONCLUSIONS: It is extremely difficult or impossible to remove remaining silicone oil from the posterior surface of a silicone IOL after short- or long-term exposure to silicone oil. This oil may interfere with the surgeon's view of the retina and may diminish the patient's visual acuity. In contrast, oil is readily removed from the posterior surface of an acrylic IOL. The authors therefore recommend the use of a soft acrylic or PMMA IOL over a silicone IOL when choosing a lens for implantation in patients who may require vitreoretinal procedures with silicone oil tamponade.

Sustained closure of surgically repaired macular holes after retinal detachment with submacular fluid.

PURPOSE: To examine the behavior of surgically repaired macular holes when subsequent retinal detachment with submacular fluid develops and to correlate these observations with current theories of macular hole formation and closure. METHODS: We reviewed the medical records of four patients who underwent successful surgical closure of macular holes and subsequently developed rhegmatogenous retinal detachment with macular involvement. RESULTS: No reopening of the original macular hole occurred in any of the four patients. No focal macular attachment was seen that would suggest firm adherence of the macular hole edges to the underlying retinal pigment epithelium. CONCLUSIONS: When retinal detachment with submacular fluid develops in patients with a successfully closed macular hole, sustained closure of the macular dehiscence is typically seen. These findings support reapproximation of the hole edges with an associated retinal wound healing response as the mechanism of hole closure.

Intravitreal sustained release corticosteroid-5-fluoruracil conjugate in the treatment of experimental proliferative vitreoretinopathy.

PURPOSE: Proliferative vitreoretinopathy (PVR) remains the most common cause of failed retinal detachment (RD) surgery. The authors compared the effectiveness of two intraocular sustained-release codrugs in suppressing PVR in a rabbit model a surgically implantable pellet releasing 5-fluorouracil (FU) and dexamethasone (DX) for 1 week and an injectable intravitreal sustained-release suspension releasing 5-FU and triamcinolone acetonide for 1 month. METHODS: Sustained-release devices and suspensions were prepared to deliver equimolar quantities of corticosteroid and 5-FU. In group 1, devices were implanted surgically into the vitreous of the right eye of 10 New Zealand White rabbits. Ten control rabbits received surgical implantation of the suture only. In group 2, drug suspension was injected into the vitreous of the right eye of 10 New Zealand White rabbits. Ten control rabbits received injection of the vehicle only. One day later, each rabbit was injected intravitreally with 250,000 homologous rabbit dermal fibroblasts. Severity of PVR was graded clinically by two masked observers on days 3, 7, 10, 14, 21, and 28. RESULTS: In group 1, clinical severity of PVR was less in the experimental group than in the control group at all time points, this was only statistically significant on day 10 (P = 0.04). Six eyes developed moderate to severe tractional RD or bullous RD in the control group by day 10 compared with none in the experimental group (P = 0.01). In group 2, the median clinical grading of eyes in the experimental group was significantly less than that in the control group at all time points through day 21 (P < or = 0.01). CONCLUSIONS: Both the intravitreal sustained-release dexamethasone-5-FU device and the triamcinolone-5-FU suspension effectively inhibit the progression of PVR in a rabbit model. Simultaneous delivery of 5-FU and corticosteroid may target different components of the wound-healing process in this disease.

Ocular toxicity following high dose chemotherapy and autologous transplant.

A 49-year-old woman received an autologous transplant for breast cancer. Six weeks later she noticed visual disturbance of the left eye which correlated with a visual field abnormality. There was a milder degree of visual disturbance in the right eye. Treatment with high-dose steroids partially stabilized the problem, which was felt to be an ischemic optic neuropathy. She ultimately died of respiratory failure. Pathology of the optic nerves revealed demyelination. Visual disturbances following high-dose chemotherapy are uncommon; the pathology to date has not been elucidated. Steroid therapy may be useful.

Tissue plasminogen activator for preserving inferior peripheral iridectomy patency in eyes with silicone oil.

PURPOSE: An inferior peripheral iridectomy (IPI) was used to prevent forward migration of silicone oil in vitrectomized eyes; however, in approximately one third of eyes, the IPI closed spontaneously. Occlusion of the IPI by fibrin is believed to be an early event in permanent IPI closure by scar tissue. The authors determined whether intraocular tissue plasminogen activator (tPA) would restore and maintain IPI patency in eyes that had early occlusion of the IPI by fibrin. METHODS: Between November 1993 and January 1995, 12 patients who underwent vitrectomy with silicone tamponade and IPI for complicated retinal detachment received an anterior chamber injection of tPA (6.25 or 12.5 microgram) for occlusion of the IPI by fibrin. RESULTS: All 12 patients had lysis of fibrin and maintained a patent IPI at the last follow-up (124+/-95 days). One patient required multiple tPA injections for recurrent fibrin formation. In another patient, a small hyphema developed after the tPA injection, which did not occlude the IPI. When compared with the natural course in a very similar group of patients previously reported, tPA had a statistically significant beneficial effect in the maintenance of IPI patency (P = 0.040). CONCLUSIONS: Intraocular tPA can be safely used to lyse postoperative fibrin occluding the IPI in eyes with silicone oil tamponade. Early lysis of this fibrin maintains IPI patency.

Cytomegalovirus retinitis associated with Hodgkin's disease.

BACKGROUND: Patients with intraocular involvement by Hodgkin's disease may present with a variety of ocular abnormalities. Intraocular infections also have been reported in these patients, including two cases of cytomegalovirus retinitis (CMV) diagnosed on postmortem examination. It often is difficult to differentiate between these conditions on clinical examination. METHODS: A patient with Hodgkin's disease presented with an atypical retinitis, vasculitis, and a serous macular detachment. Results of clinical examination, fluorescein angiography, and vitreous biopsy for culture and polymerase chain reaction (PCR) testing are described. RESULTS: The diagnosis of an atypical CMV retinitis simulating possible intraocular involvement by Hodgkin's disease was confirmed by PCR testing of undiluted vitreous. Intravenous therapy with foscarnet, guided by the results of the vitreous biopsy, resulted in resolution of the retinitis and an improvement in vision. CONCLUSION: Intraocular involvement by cytomegalovirus retinitis can simulate intraocular lymphoma in a patient with Hodgkin's disease Polymerase chain reaction testing was useful in establishing the diagnosis and guiding successful therapy in this patient.

Treatment of migraine headache after ocular surgery with intravenous metoclopramide hydrochloride.

PURPOSE: To alert ophthalmologists that prolonged or severe postoperative periocular pain and nausea may be caused by migraine. METHODS: We examined two patients who had a history of migraine and had severe episodes of prolonged periocular pain and nausea after ocular procedures. Both patients experienced symptoms similar to their previous migraine attacks. In neither was pain alleviated by routine analgesics. RESULTS: Each patient had relief of symptoms within two minutes after intravenous delivery of metoclopramide hydrochloride. CONCLUSIONS: Ophthalmologists should consider the diagnosis of postoperative migraine in similar patients and provide specific therapy such as intravenous metoclopramide hydrochloride.

Retinopathy and optic neuropathy in bone marrow transplantation for breast cancer.

PURPOSE: To characterize the ocular toxicity of a bone marrow transplant regimen does not include total body or focal head irradiation. METHODS: Nine patients with advanced breast cancer were referred for visual symptoms after high-dose chemotherapy with cisplatin, cyclophosphamide, and carmustine and autologous bone marrow transplantation without total body irradiation or local head irradiation. RESULTS: Symptoms consistent with optic neuropathy and retinopathy developed in five patients. Retinopathy alone developed in three patients and optic neuropathy alone developed in one. Retinal abnormalities included cotton-wool spots, intraretinal hemorrhages, and macular exudate. Optic nerve findings included disk swelling and subsequent pallor. Symptoms and signs associated with retinopathy were generally reversible, whereas those associated with optic neuropathy often were permanent. Retinopathy and/or optic neuropathy developed in all of the patients from 1 to 5 months after bone marrow transplantation. Resolution or stabilization of findings was observed 2-4 months after presentation. Two patients with optic neuropathy showed progression of field and acuity loss after 4 months. When compared with control subjects, the exposure of patients to cyclophosphamide and carmustine was no different. However, cisplatin exposure was 1.2-fold higher in patients with ocular toxicity compared with control subjects. CONCLUSION: Optic neuropathy and retinopathy are presumed to arise from the administration of a high-dose chemotherapy regimen. As techniques in supportive care improve, long-term adverse effects of these therapies now are becoming apparent.

Monocyte-induced cytokine expression in cultured human retinal pigment epithelial cells.

Monocytes and retinal pigment epithelial cells are intimately associated in membranes of eyes with proliferative vitreoretinopathy and in certain types of uveitis. The goal of this study was to determine whether monocytes modulate cytokine expression in retinal pigment epithelial cells, and if so, to identify the monocyte products responsible for this effect. Cultured human retinal pigment epithelial cells were exposed to varying concentrations of monocyte-conditioned medium from unstimulated human monocytes for 1-48 hr, or from monocytes prestimulated with lipopolysaccharide. mRNA expression of interleukin-1 beta, interleukin-6, interleukin-8, melanoma growth stimulating activity/gro alpha and gamma, macrophage colony stimulating factor, transforming growth factor-beta 2, basic fibroblast growth factor and activin beta A chain was determined by reverse transcription polymerase chain reaction. Protein secretion of selected cytokines, interleukin-1 beta, interleukin-6, interleukin-8, macrophage colony stimulating factor and transforming growth factor-beta 2 was measured in RPE-conditioned medium by ELISA. Retinal pigment epithelial cells constitutively expressed mRNA for interleukin-6, macrophage colony stimulating factor, transforming growth factor-beta 2, basic fibroblast growth factor and activin beta A chain. Interleukin-1 beta, melanoma growth stimulating activity/gro alpha and gamma and interleukin-8 were not expressed under basal conditions. Stimulated monocyte-conditioned medium markedly induced mRNA of all cytokines except basic fibroblast growth factor and transforming growth factor-beta 2 in a dose- and time-dependent manner. Unstimulated monocyte-conditioned medium was a less potent inducing agent, but still enhanced mRNA expression of interleukin-6, interleukin-8 and melanoma growth stimulating activity/gro alpha. Stimulated monocyte-conditioned medium also induced a time-dependent increase in interleukin-6, Interleukin-8, macrophage colony stimulation factor and transforming growth factor-beta 2, but not interleukin-1 beta protein secretion (p < 0.05 for all time points). Neutralizing antibodies to interleukin-1 beta, or tumour necrosis factor alpha, but not interleukin-1 alpha, significantly reduced cytokine mRNA expression induced by stimulated monocyte-conditioned medium. The combination of all three neutralizing antibodies almost entirely eliminated monocyte-induced mRNA expression and protein production of all cytokines studied. Activated monocytes secrete a heterogeneous mixture of products that together strongly induce expression of multiple cytokines in human retinal pigment epithelial cells. Most if not all of the inducing effect can be accounted for by interleukin-1 beta and tumour necrosis factor alpha. Because cytokines have been implicated in proliferative vitreoretinopathy and uveitis, monocyte-mediated cytokine expression by RPE cells may serve to initiate and perpetuate these diseases.