Thermoradiotherapy of intraocular tumors in an animal model: concurrent vs. sequential brachytherapy and ferromagnetic hyperthermia.

PURPOSE: To compare concurrent vs. sequential ferromagnetic thermoradiotherapy in vivo. METHODS AND MATERIALS: Greene melanomas were implanted subretinally in rabbits and observed until they were 3-5 mm in diameter. Episcleral plaques were assembled with 125I seeds for radiation therapy, or with ferromagnetic (FM) thermoseeds and nonradioactive I seeds for hyperthermia. Rabbits were implanted by centering a plaque over the intraocular melanoma. After a given dose of radiation had been delivered, the plaque was removed and a nonradioactive plaque containing FM thermoseeds was inserted into the same extrascleral space. One hour later, hyperthermia (46-47 degrees C at the plaque-scleral interface) was initiated and continued for a period of 1 h by placing the rabbits in a magnetic induction coil powered to 1200 W. Tumor size was determined at 1- to 2-week intervals by indirect ophthalmoscopy and by ultrasound. RESULTS: Dose-response analysis of 27 treated eye melanomas showed 50% local tumor control at 43 Gy for 125I alone and 29.4 Gy for 125I followed by FM hyperthermia. The thermal enhancement ratio was 1.4. CONCLUSION: Comparison with a previously published thermal enhancement ratio of 4.4 (for concurrent 125I and FM hyperthermia) leads us to conclude that thermal enhancement of 125I brachytherapy is more efficient in this tumor model system when hyperthermia is delivered during, rather than after, the irradiation process.

A new technique for subchoroidal implantation of experimental malignant melanoma.

A new technique for implanting Greene hamster amelanotic melanoma cells into the rabbit eye is described. The technique involves the deposition of a tumor fragment into the subchoroidal space via a transvitreal approach. Thirty rabbit eyes were implanted with 26 successful tumor growths producing solitary choroidal nodules. This technique offers the advantages of rapid implantation, the ability to precisely choose the site of implantation including posterior sites, and eliminates the need for a large scleral incision.

In vitro efficacy of carboplatin and hyperthermia in a murine retinoblastoma cell line.

PURPOSE: To determine the cell-killing activity of varying doses of carboplatin, graded hyperthermia, and the combination of carboplatin and hyperthermia in the treatment of a transgenic murine retinoblastoma cell line. METHODS: Replicate cell wells (more than six wells per dose point) from an established transgenic murine retinoblastoma cell line (Rb-6) were exposed to a single application of hyperthermia for 15, 30, 60, and 120 minutes at temperatures of 37 degrees C (control), 40 degrees C, and 43 degrees C. Carboplatin dose response treatment was studied at doses of 2000, 1000, 500, 400, 300, 200, 100, and 50 ng per well. Combined treatment studies used these carboplatin dosages with each of the graded hyperthermia exposure temperatures at each exposure time. At 24 hours, all wells were pulsed with 3H-thymidine for 24 hours, washed three times, harvested, and counted. Raw counts (3H-thymidine) were fitted to a linear regression model to calculate the lethal dose for 50% (LD50) of cells. RESULTS: The LD50 for carboplatin exposure at 37 degrees C occurred at 542 ng. The LD50 for hyperthermia at 40 degrees C occurred at 90 minutes and at 43 degrees C it occurred at 62 minutes. Combined hyperthermia and carboplatin exposure yielded a synergistic interaction with an LD50 of 327 ng at 43 degrees C for 30 minutes. Determination of a thermal enhancement ratio yielded an enhancement range of 1.1 to 25.8. CONCLUSIONS: The synergistic cytocidal interaction of heat and carboplatin in a transgenic murine retinoblastoma cell line has been established in this study. The increased thermal enhancement ratio documents the potential utility of combined treatment applications in reducing treatment levels of single-modality therapy, potentially allowing for a decrease in treatment-related morbidity.

Management of ectopia lentis in a family with Marfan syndrome.

OBJECTIVE: To determine the effectiveness of combined pars plana vitrectomy-lensectomy and open-loop anterior chamber lens implantation for the management of ectopia lentis associated with Marfan syndrome. METHODS: Retrospective review of the medical records of 4 consecutive patients with Marfan syndrome who underwent combined pars plana lensectomy-vitrectomy and anterior chamber lens implantation at our institution between August 1994 and July 1995. RESULTS: All patients demonstrated postoperative visual acuity of 20/25 or better during an average follow-up period of 6 months (range, 4-9 months). Two patients developed pseudophakic pupillary block and required YAG laser iridotomy postoperatively. CONCLUSIONS: Pars plana lensectomy-vitrectomy and anterior chamber intraocular lens implantation appears to be an excellent technique for the management of ectopia lentis associated with Marfan syndrome. A bimanual, closed-system endosurgical technique avoids many of the complications previously associated with surgery for ectopia lentis.

Echographic diagnosis of anterior hyaloidal fibrovascular proliferation.

High-resolution contact B-scan echographic imaging of the ciliary body and peripheral retina was performed on five eyes with anterior hyaloidal fibrovascular proliferation and media opacity by means of a wide (58 degrees) scanning arc. This technique determined the circumferential and anteroposterior extent of peripheral traction retinal detachment associated with anterior hyaloidal fibrovascular proliferation, which correlated highly with findings at subsequent vitrectomy. Final visual acuity of 20/400 or better was achieved in the two eyes (50%) with more limited peripheral traction detachment. In the presence of media opacity, anterior echographic imaging may allow early detection of traction retinal detachment associated with anterior hyaloidal fibrovascular proliferation and may be useful in characterizing the severity of this condition.

2 peripheral scatter photocoagulation for neovascularization associated with pars planitis.

BACKGROUND: Peripheral cryotherapy appears to be efficacious in the treatment of neovascularization of the vitreous base in patients with pars planitis, although it may be associated with the development of rhegmatogenous retinal detachments. OBJECTIVE: To evaluate the safety and efficacy of peripheral scatter photocoagulation for treatment of neovascularization of the vitreous base when used alone or combined with pars plana vitrectomy. METHODS: Six patients (10 eyes) presented with vitritis, cystoid macular edema, and neovascularization of the vitreous base, unresponsive to corticosteroid therapy. Three patients (five eyes) received scatter diode or argon photocoagulation treatment alone. The other three patients (five eyes) underwent pars plana vitrectomy coupled with argon or diode photocoagulation, placed in three rows, posterior to the area of inferior neovascularization of the vitreous base. RESULTS: Pretreatment visual acuity ranged from 20/20 to 20/200. All patients were followed up for a minimum of 6 months. After placement of photocoagulation (with or without concurrent pars plana vitrectomy), the neovascularization regressed, inflammation was stabilized, and cystoid macular edema improved in all eyes. There were no retinal detachments or other complications of treatment. Posttreatment visual acuity ranged from 20/20 to 20/100. When final visual acuity was 20/40 or less, cataract formation was generally responsible. CONCLUSIONS: Peripheral scatter photocoagulation is efficacious and appears at least equal to peripheral cryotherapy in causing regression of neovascularization of the vitreous base in patients with pars planitis.

Golf-related ocular injuries.

OBJECTIVE: To review golf-related ocular injuries, which account for 1.5% to 5.6% of all sports injuries. METHODS: During 8 years (1986 to 1994), a retrospective review of sports-related trauma was performed at the Medical College of Wisconsin, Milwaukee. Eight blunt ocular injuries (four ruptured globes and four globes without rupture) caused by golf-related activities were identified. The four ruptured globes caused by golf-related trauma accounted for 1.2% of all penetrating injuries and/or ruptured globes and 11.7% of sports-related injuries. RESULTS: A golf ball projectile was the mechanism of injury in six patients, while two patients were struck with a gold club. The four patients with ruptured globes had an initial visual acuity of light perception or worse, and three globes were subsequently enucleated, while one was prephthisic. In the four trauma cases without rupture, surgical intervention was required to achieve anatomic stability, with final visual acuities ranging from 20/25 to 20/40. CONCLUSIONS: The incidence of ocular injuries caused by golf-related trauma is low compared with that for other sports-related injuries. Although the prognosis for ruptured globes occurring in this setting remains extremely guarded, blunt trauma without rupture caused by a golf-related injury is associated with a more favorable visual and anatomic outcome.

Echographic verification of radioactive plaque position in the treatment of melanomas.

Visualization of the position of an episcleral plaque in relation to the underlying choroidal melanoma during the early radiation treatment period reconfirms accurate plaque location and may help assure optimal treatment. We used high-resolution B-scan echography to confirm the position of the episcleral plaque in 16 consecutive cases of choroidal melanoma. The technique is most useful for well-defined tumors as small as 3 mm in height whose anterior border does not extend beyond the ora serrata.

Illuminated retinal picks for vitreous surgery.

We developed a new illuminated disposable retinal pick system for use in vitreoretinal surgery. These instruments facilitate bimanual dissection of proliferative tissue while allowing ocular endoillumination. We have found these instruments to be helpful in the management of complicated retinal detachment due to proliferative diabetic retinopathy or proliferative vitreoretinopathy.

Ruptured globes following radial and hexagonal keratotomy surgery.

OBJECTIVE: To ascertain if cases of radial keratotomy wound rupture were occurring and whether the globes ruptured through the corneal incisions. DESIGN: Cases of traumatic ruptured globe after incisional corneal refractive surgery were collected from ophthalmologists and from peer-reviewed and other ophthalmic literature. RESULTS: Twenty-eight human eyes (eight previously unreported) are known to have ruptured through refractive corneal incisions in activities of daily living (n = 12), assault (n = 7), motor vehicle accidents (n = 5), and sports (n = 4). Two patients died of their injuries. Of the remaining 26 ruptured eyes, eight (31%) recovered 20/40 or better visual acuity. Six eyes (23%) were totally blinded, six (23%) were legally blinded, and six (23%) had best corrected visual acuity of 20/40 to 20/100 despite multiple surgical procedures. CONCLUSIONS: As radial keratotomy becomes more popular the pool of patients who may experience traumatic ruptured globe will grow. Every patient who has had radial keratotomy should be aware that the surgery has weakened the eye(s).

Ferromagnetic hyperthermia and iodine 125 brachytherapy in the treatment of choroidal melanoma in a rabbit model.

Hyperthermia has been combined with conventional radiation methods to achieve enhanced tumor destruction. We combined iodine 125 seeds with ferromagnetic thermoseeds in a single plaque to simultaneously deliver radiation and heat in a rabbit model of choroidal melanoma. Initially, six ferromagnetic thermoseeds were placed in parallel on a 14-mm episcleral plaque. The plaques were placed on normal rabbit eyes and on eyes containing transvitreally implanted choroidal melanoma. The heating response was assessed in both normal and tumor-containing eyes. Rigid copper-constantan and flexible Baily thermocouples were used to monitor temperature responses. The animals were subjected to an electromagnetic field of 100 kHz, with power of 1100 to 1500 W. The thermoseeds autoregulated at 48.2 degrees C. Scleral temperatures stabilized at 45.8 degrees C +/- 0.4 degrees C (SD), while temperatures at the base of the tumor stabilized at 43.6 degrees C +/- 0.1 degrees C. Ferromagnetic thermoseeds were then combined with iodine 125 seeds. Similar temperature responses were recorded, and autoradiographic findings confirmed a uniform radiation distribution. Varying the amount or type of ferromagnetic material in the thermoseeds allows the delivery of heat at virtually any temperature. Ferromagnetic hyperthermia may provide a more simplified approach over currently available methods of heat delivery.

Retinopathy progression and visual outcomes after phacoemulsification in patients with diabetes mellitus.

OBJECTIVES: To determine the rate of progression of diabetic retinopathy after phacoemulsification surgery, and whether surgeon experience and/or surgical duration adversely affect visual outcome. METHODS: A retrospective review of 150 eyes of 119 diabetic patients who underwent phacoemulsification surgery during a 5-year period was performed. Data collected included patient age, sex, type and duration of diabetes, diabetic control, associated systemic health factors, preoperative visual acuity and retinopathy grade, duration of surgery, intraoperative complications, and postoperative course. The effect of these factors on visual outcome and rate of retinopathy progression was studied by means of univariate and stepwise multivariate logistic regression analyses. Resident and private cases were compared. RESULTS: Visual acuity improved by 2 or more lines in 117 eyes (78%); 93 eyes (62%) had a final visual acuity of at least 20/40. Retinopathy progression was seen in 37 eyes (25%) with 6 to 10 months of follow-up. Preoperative nonproliferative diabetic retinopathy, proliferative diabetic retinopathy, and limited surgical experience were statistically associated with retinopathy progression and poor visual outcome. CONCLUSIONS: The visual results and rate of retinopathy progression after phacoemulsification surgery in our series did not differ significantly from those reported that used other techniques. Nonproliferative and proliferative diabetic retinopathy and surgical inexperience resulted in an increased rate of retinopathy progression. Arch Ophthalmol. 2000;118:912-917

Ocular injuries caused by elastic cords.

Five patients with ocular trauma due to elastic cords with attached metal or plastic hooks were evaluated over a 13-month period. Injuries included hyphema, angle recession, lens subluxation, choroidal rupture, vitreous hemorrhage, retinal detachment, and scleral rupture. Two patients suffered penetrating ocular injuries, and three patients had final visual acuities of 20/200 or less. This series emphasizes the potential severity of ocular injury due to these commonly used devices and reiterates a modification in design that might decrease the likelihood of accidental trauma from elastic cords.

Combined phacoemulsification, pars plana vitrectomy, and posterior chamber intraocular lens insertion.

Eighteen eyes with coexisting cataract and vitreoretinal disease underwent combined phacoemulsification, pars plana vitrectomy, and posterior chamber lens implantation. Preoperative vitreoretinal disease included nonclearing vitreous hemorrhage (eight eyes), vitreous hemorrhage and tractional retinal detachment (three eyes), tractional retinal detachment (one eye), epiretinal membranes (three eyes), peripheral uveitis (two eyes), and a retained intraocular metallic foreign body (one eye). Postoperative visual acuity improved in each case; 14 eyes achieved visual acuity between 20/20 and 20/80 during an average postoperative period of 11 months (range, 3 to 39 months). Perioperative complications included an iatrogenic retinal break (one eye) and pupillary block glaucoma (one eye). Four eyes required YAG laser capsulotomy postoperatively. Phacoemulsification did not interfere with corneal clarity, allowed water-tight wound closure during vitrectomy, and preserved the capsular bag, allowing endocapsular fixation of the posterior chamber lens. Combining phacoemulsification, posterior chamber lens implantation, and pars plana vitrectomy allows rapid visual rehabilitation and functional unaided vision in these eyes.

Vitrectomy for traumatic retinal incarceration.

Traumatic retinal incarceration into a scleral wound may prevent successful surgical rehabilitation of eyes with severe posterior segment injury. We managed 15 consecutive eyes with traumatic retinal incarceration and associated retinal detachment with vitrectomy techniques. We based our approach on the anteroposterior location of the incarceration site and the amount of retina incarcerated into the wound. Despite successful anatomic reattachment in six of seven eyes with retinal incarceration posterior to the vortex vein ampullae, only two of seven eyes achieved visual acuity of 5/200 or better. In eyes with more peripheral retinal incarceration, anatomic reattachment was achieved in five of eight eyes and visual acuity of 5/200 or better was achieved in four eyes. Overall, a visual acuity of 5/200 or better was achieved in six (40%) of 15 eyes with a minimum follow-up of six months.

Management of traumatic hemorrhagic retinal detachment with pars plana vitrectomy.

Traumatic hemorrhagic retinal detachment may prevent successful visual rehabilitation of eyes with severe posterior segment injury. We managed 19 consecutive cases of traumatic hemorrhagic retinal detachment with pars plana vitrectomy, scleral buckling, and fluid-gas exchange, with or without internal drainage of subretinal hemorrhage. We based our approach on the amount of subretinal hemorrhage present and the location of associated retinal breaks. Internal drainage of subretinal hemorrhage was performed in 16 eyes to allow adequate retinopexy to hemorrhagically elevated retinal breaks (9 eyes), to remove massive subretinal hemorrhage (4 eyes), and to allow intraoperative reattachment when the retina exhibited bullous retinal detachment (3 eyes). Overall, with a minimum of 6 months of follow-up, anatomic reattachment was achieved in 13 (68%) of 19 eyes, and functional success (visual acuity 5/200 or better) was achieved in 6 (32%) of 19 eyes. Anatomic failure resulted from proliferative vitreoretinopathy (4 eyes) and globe atrophy (2 eyes). Drainage of subretinal blood appeared to be beneficial for hemorrhagically elevated retinal tears to allow adequate retinopexy and may help to accomplish long-term anatomic attachment in eyes with massive subretinal hemorrhage or bullous retinal detachment.

A two-stage technique for intraoperative fluid-gas exchange following pars plana vitrectomy.

We describe herein a two-stage technique of intraoperative fluid-gas exchange following pars plana vitrectomy. The first stage is a complete fluid-air exchange using an air pump and intraocular linear suction. The air pump then maintains the intraocular pressure at the desired level during adjunctive procedures, such as laser endophotocoagulation. The second stage is an air-gas mixture exchange in which the desired gas, premixed in air to the desired final intraocular concentration, is manually flushed through the eye. This technique allows the attainment of an accurate concentration of intraocular gas if the air-gas mixture exchange is complete. In vitro and in vivo experiments in aphakic human eyes demonstrated that an effectively complete air-gas mixture exchange occurs with a 25-mL flush volume. This result compares favorably with the theoretical prediction derived from a "pharmacokinetic approximation" equation.

Photoablation of ocular melanoma with a high-powered argon endolaser.

We studied the use of a 15-W argon blue-green laser in the treatment of choroidal melanoma in a rabbit model. Greene melanoma cells were used to produce 2- to 4-mm thick tumors posteriorly in the suprachoroidal space in pigmented rabbits. Endophotocoagulation delivered through a 600-micron fiberoptic probe was performed to ablate the tumor tissue and a surrounding margin of normal tissue. A vitreous cutter was used simultaneously to remove liberated necrotic debris. The effect of the laser on tumor and normal ocular tissue was evaluated by light microscopy and the extent of the proliferative response by tritiated thymidine radioautography. Application of 100 to 400 pulses of laser energy using treatment parameters of 12 to 14 W of power and 0.1-s pulses resulted in complete ablation of melanoma tissue, overlying retina, and choroid. There was no substantial intraoperative or postoperative hemorrhage. Material liberated during the laser treatment was found to be nonviable. The effect of the laser on tissue appeared localized to within approximately 1.25 mm of the margin of the central lesion. The high-energy argon laser seems to offer a means of effectively ablating melanoma tissue via an internal resection approach.

A technique for facilitated visualization and dissection of the vitreous base, pars plana, and pars plicata.

We describe a technique to facilitate visualization of the vitreous base, pars plana, and pars plicata during vitreous surgery. This technique takes advantage of an externally applied fiberoptic light source coupled with scleral depression to enable direct viewing of the ciliary processes and anterior vitreous base. No special instrumentation or alteration in pars plana vitrectomy techniques is required. We have used this technique to enhance anterior dissection during vitrectomy surgery in the aphakic and pseudophakic eye associated with proliferative vitreoretinopathy, diabetic retinopathy, epithelial down-growth syndromes, and postvitrectomy fibrin formation.

Penetrating ocular injury from contaminated eating utensils.

Although the rate of infectious endophthalmitis following penetrating ocular injury is generally less than 10%, certain settings may carry a greater risk of infection. One such setting is penetrating injury resulting from eating utensils contaminated with oral flora. We reviewed six of these injuries. Culture-positive bacterial endophthalmitis developed in four of the six eyes; only one of the eyes retained reading visual acuity (greater than 20/50) and two eyes lost light perception. The potential for infection and limited visual outcome in this series warrants aggressive prophylaxis and treatment. The unexpected isolation of Haemophilus influenzae in two of the four infections suggests that broad-spectrum antibiotic treatment should be considered in all such injuries since less common organisms may be encountered.