Treatment of tumors involving the optic nerves and chiasm

An approach toward treatment of tumors involving the optic apparatus is presented. When tumors cause mass effect, microsurgical excision or debulking is generally recommended. Radiosurgery has been controversial yet advances in imaging and high speed computer planning allow treatment of lesions involving the optic apparatus with low morbidity. Microsurgical and radiosurgical approaches to tumors involving the globe, orbit, suprasellar region and third ventricle are discussed. Gamma Knife radiosurgery for choroidal melanomas spares orbital excenteration. We have used a marginal dose of 2025 Gy for choroidal melanomas and generally limit the optic nerves and chiasm to less than 10 Gy in other cases. The effective dose for cavernous hemangiomas remains unclear, however we have had success with marginal doses in the range of 1620Gy. Lower doses may prove successful yet better spare vision in cases where vision is useful. Our combined microsurgical and radiosurgical approach to tumors involving the apparatus has had an excellent rate of sparing vision, a low overall morbidity and excellent success.     

Dosis-Volumen-Histogramm-Regressionsanalyse von Aderhautmelanomen nach einzeitiger Leksell-Gamma-Knife-Radiochirurgie

Background

To evaluate tumor regression and sequelae in 30 uveal melanomas treated with Gamma Knife radiosurgery between 1992 and 1995 at the Gamma Knife center in Graz.

Patients

A total of 30 uveal and ciliary body melanomas were treated with a single fraction of the Gamma Knife. The mean marginal dose was 52.1 Gy, (median 50 Gy). Of the tumors, 15 were large (higher than 8 mm), 14 were medium sized (3–8 mm) and one was a small melanoma (<3 mm). Among them were 6 juxtapapillary, 10 (juxta-) maculary melanomas, 5 tumors located in the midperiphery and 9 ciliary body melanomas.

Method

Dose-volume histogram analysis.

Results

After a maximum follow up of 9 years and 7 months, 8 tumors regressed into a scar, 17 tumors into a residual prominence between 50% and 80% of the initial tumor height, 3 tumors showed no change and in 2 patients recurrence was obvious. Sequelae were classified as mild (in 3 patients), moderate (3), severe (5) and very severe (19).

Conclusions

Significant factors for the development of severe sequelae were the tumor volume and the marginal dose, the mean dose proved to be more important than the marginal dose and the irradiated volume more important than the selective critical dose.     

Dose-volume histogram regression analysis of uveal melanomas after single fraction gamma knife radiosurgery

BACKGROUND: To evaluate tumor regression and sequelae in 30 uveal melanomas treated with Gamma Knife radiosurgery between 1992 and 1995 at the Gamma Knife center in Graz. PATIENTS: A total of 30 uveal and ciliary body melanomas were treated with a single fraction of the Gamma Knife. The mean marginal dose was 52.1 Gy, (median 50 Gy). Of the tumors, 15 were large (higher than 8 mm), 14 were medium sized (3-8 mm) and one was a small melanoma (<3 mm). Among them were 6 juxtapapillary, 10 (juxta-) maculary melanomas, 5 tumors located in the midperiphery and 9 ciliary body melanomas. METHOD: Dose-volume histogram analysis. RESULTS: After a maximum follow up of 9 years and 7 months, 8 tumors regressed into a scar, 17 tumors into a residual prominence between 50% and 80% of the initial tumor height, 3 tumors showed no change and in 2 patients recurrence was obvious. Sequelae were classified as mild (in 3 patients), moderate (3), severe (5) and very severe (19). CONCLUSIONS: Significant factors for the development of severe sequelae were the tumor volume and the marginal dose, the mean dose proved to be more important than the marginal dose and the irradiated volume more important than the selective critical dose.     

Effect of radiation dose on ocular complications after iodine brachytherapy for large uveal melanoma: empirical data and simulation of collimating plaques

PURPOSE: To calculate radiation doses to intraocular tissues in iodine brachytherapy (IBT) for large uveal melanoma, to study their relationship to ocular complications, and to assess a modified plaque design to reduce doses to the macula and optic nerve. METHODS: Ninety-six patients with a uveal melanoma, classified as large according to the Collaborative Ocular Melanoma Study criteria, underwent primary IBT. Median tumor height and diameter were 10.7 (range, 4.5-16.8) and 16.5 (range, 7.3-25.0) mm, respectively, and median follow-up was 3.5 years (range, 0.3-10.4). Each IBT was retrospectively modeled with a plaque simulator to calculate doses and dose rates to ocular tissues. Cox proportional hazards regression was used to assess their association with time to ocular complications, low vision, and blindness (20/70 or worse and loss of 20/400, respectively). A collimating plaque design was assessed by replacing the actual plaque with the modified one in each model. RESULTS: Median doses to tumor apex and base were 81 (range, 40-158 Gy) and 384 (range, 188-1143) Gy, respectively, and the median dose rates at these points were 53 (range, 11-204) and 289 (range, 84-1213) cGy/h, respectively. Median doses to the lens, macula, and optic disc were 69 (range, 20-141), 79 (range, 12-632), and 83 (range, 10-377) Gy, respectively. Dose to the lens was associated with cataract (hazard ratio [HR] 1.15 for each 10-Gy increase, P = 0.002), and dose to the optic disc with optic neuropathy (HR 1.08, P = 0.001). Dose to the macula predicted low vision (HR 1.06, P = 0.025) and blindness (HR 1.10, P < 0.001). A collimating design provided a median reduction of 36 (range, +19 to -198) and 30 (range, +9 to -160) Gy in modeled doses to the macula and optic disc, respectively. CONCLUSIONS: Simulated dose distribution together with tumor height predicts major complications and vision loss after IBT. Simulation suggests that clinically meaningful dose reduction to normal tissues is feasible with a redesigned brachytherapy protocol, which may help to reduce complications and vision loss after IBT of large uveal melanoma.     

DNA cell cycle studies in uveal melanoma

We histologically studied uveal melanomas treated with surgery only (enucleation or ciliochoroidectomy), low-dose (20 Gy) preenucleation radiation followed by enucleation, or enucleated melanomas after high-dose (50 to 80 Gy) charged-particle beam therapy. There was significantly less bromodeoxyuridine uptake in irradiated vs nonradiated melanomas (P less than .0001). Similarly, tissue culture growth of irradiated tumors was significantly less (P less than .007). These data demonstrate destruction of reproductive integrity of helium ion-irradiated melanomas. The incorporation of bromodeoxyuridine and fine needle aspiration biopsy techniques may be useful in the delineation of successfully irradiated tumors from tumors with apparent growth secondary to radiation vasculopathy.     

Treatment of choroid melanoma with a radioactive iodine 125 plaque: initial results of a pilot study

The present paper reports on the treatment of 9 choroidal melanomas with a prominence of 5 to 8.7 mm, using iodine-125 plaque. Follow-up: 1-1 3/4 years. Radiation dose per hour: 0.3-0.6 Gy, tumor apex 70 Gy, tumor basis 370 Gy; plaque in situ 1 to 2 weeks. Localization of tumor: 2 X close to macula, 2 X extending into macula, 1 X 1 mm from disc. Postoperative regression of all 9 melanomas, by 51% after 1 year. Postoperatively no reduction in bulbus size, rubeosis iridis, cataract, or optic atrophy; however, 2 X reduced visual acuity: 1 X temporary (increase after laser coagulation of neovascularization), 1 X permanent (discrete subretinal gliosis in residual macular half not extending into radiation scar). Visual acuity 6 months postoperatively equal to that after 1-1 3/4 years and in 5 out of the 9 patients 20/100 to 20/30. An attempt is made to correlate the anatomical and functional results with the "tumor surgery in small steps" achieved with iodine-125 plaquing.     

Tuberculum sellae meningioma associated with lymphomatoid papulosis.

BACKGROUND: Meningiomas involving the tuberculum sellae and planum sphenoidale typically cause visual loss by affecting the optic nerve and anterior chiasm. We present a case of a tuberculum sellae meningioma concurrent with lymphomatoid papulosis, a T-cell lymphomatoid skin disorder. CASE REPORT: A 50-year-old black woman came to the eye clinic with a symptom of decreased vision in the right eye for one week, especially when reading. Best-corrected vision was counting fingers at two feet O.D. and 20/40 O.S. She was seen seven months earlier, with 20/25 O.D. and O.S. Dilated fundus examination revealed bilateral optic atrophy, O.D. greater than O.S. MRI revealed a meningioma arising from the tuberculum sellae and planum sphenoidale region. The meningioma was partially resected nine days later Visual field performed 18 days postoperatively demonstrated an overall depression in the right eye and no defect in the left eye. Best-corrected vision improved to 20/150 O.D. and 20/30 O.S. CONCLUSION: Meningiomas are generally benign tumors that can cause symptoms if vital structures are compromised. Altered visual function and optic atrophy may be the only presentation of intracranial and orbital tumors. Intracranial meningiomas may be associated with systemic conditions that can infiltrate the optic nerve, including lymphocytic disorders. Lymphomatoid papulosis (LyP) is a rare cutaneous disorder involving infiltrating clonal T-cells that has been associated with disseminated lymphomatic skin tumors. It is unclear if there is a direct association between LyP and meningiomas.     

Transpupillary thermotherapy for choroidal melanoma.

The management of choroidal melanomas depends on many factors, most importantly, tumor size and location. Small choroidal melanoma in the posterior fundus is amenable to treatment options such as enucleation, radiotherapy, laser photocoagulation, and transpupillary thermotherapy or a combination of these methods. Transpupillary thermotherapy is a technique of tumor heating by infrared radiation delivered through the pupil into the tumor. This method causes dramatic tumor necrosis in choroidal melanomas up to 4 mm in thickness. With properly selected small choroidal melanomas, tumor control is approximately 94%. The heat induces cellular damage at the site of treatment with few remote side effects; therefore, complications are generally limited to the site of treatment and include retinal vascular obstruction (23%), retinal traction (20%), retinal neovascularization (6%), and retinal hole with detachment (< 1%). Tumors located temporal to the foveola demonstrate a statistically higher risk for retinal traction than those located in other quadrants. Tumors near the optic disk demonstrate a higher incidence of retinal neovascularization due to heat-induced obstruction of a major retinal vascular arcade. Overall, vision preservation is satisfactory after thermotherapy for choroidal melanoma, with more than 50% of patients maintaining the same or better vision after treatment, depending primarily on tumor location. In summary, small choroidal melanomas can be controlled with transpupillary thermotherapy, especially those near the optic disk and foveola in areas that are otherwise difficult to irradiate. Longer follow-up is necessary to assess for local recurrence and the impact of treatment on life prognosis.     

Radiation effects on the optic nerve observed after brachytherapy of choroidal melanomas with 106Ru/106Rh plaques

From 1966 to 1990 a total of 93 juxtapapillary choroidal melanomas were treated using ¹⁰⁶Ru/¹⁰⁶Rh plaques with a notch for the optic nerve. The choroidal melanoma was controlled after brachytherapy in 79 cases (85%). Fourteen eyes (15%) had to be enucleated because of tumor regrowth. Eye and optic nerve phantoms were fabricated, loaded with small-volume thermoluminescent dosimeters, treated with active plaques, and the radiation dose determined at the optic disc and along the optic nerve. The median dose within the anterior optic nerve was 51.2 Gy (range 10.3–60.5 Gy). The probability of developing complete radiation optic-neuropathy (RON) was 23% and 53% at 5 and 10 years, respectively. The probability of developing partial RON was 66% at 5 years and 82% at 10 years. The probability of retaining visual acuity better than 0.5 was 38% at 5 years and 26% at 10 years. No dose-response relationship could be established from the ophthalmological, morphological and functional findings. Eyes following plaque irradiation with 50 Gy or more in the center of the optic nerve experienced significant radiation optic neuropathy, other eyes did not.Presented at the 18th Meeting of the Club Gonin, Vienna, 6–10 September 1992     

Palladium-103 plaque radiotherapy for choroidal melanoma: results of a 7-year study

OBJECTIVE: To describe the first clinical experience with palladium-103 (103Pd) ophthalmic plaque radiotherapy for choroidal melanoma. DESIGN: Phase-I (nonrandomized) clinical trial. PARTICIPANTS: Eighty patients with uveal melanomas were diagnosed by clinical examination, found to be negative for metastatic disease, and offered 103Pd radioactive plaque treatment. Nine patients were concurrently treated with microwave hyperthermia. INTERVENTION: Palladium-103 ophthalmic plaque radiotherapy was employed for each patient. Eye plaques were sewn to the episclera to cover the base of the intraocular tumor, radiation was continuously delivered over 5 to 7 days, and then the plaques were removed. A mean apical dose of 81 Gy was delivered. MAIN OUTCOME MEASURES: The authors evaluated the ease of use of 103Pd seeds within standard gold eye plaques. Patient-related outcomes were control of tumor growth, change in visual acuity, the development of radiation damage (retinopathy, optic neuropathy, and cataract), and metastatic disease. RESULTS: From September 1990 to December 1997, 80 patients were treated with 103Pd and followed for an average of 38 months. Two patients were lost to follow-up. During this time, the authors found that 103Pd seeds were equivalent to iodine-125 (125I) with respect to plaque manufacture and ease of dosimetric calculations. Two patients in this series were treated for tumor recurrence after 125I plaque radiotherapy. They both failed secondary 103Pd treatment and were enucleated. When 103Pd was used as a primary treatment, it controlled the growth of 75 of 78 tumors (96%). Overall, there have been six enucleations: three failures of primary treatment, two failures of retreatment, and one for neovascular glaucoma. Visual acuity evaluations at the 36-month follow-up visit (including the enucleated patients) revealed that 38% of eyes had decreased 3 or more lines of vision, and 77% were 20/200 or better. CONCLUSION: Palladium-103 plaque radiotherapy can be used to treat uveal melanomas. Compared with 125I, computerized dosimetry suggests a more favorable dose distribution with 103Pd. Treatment of most patients resulted in tumor shrinkage and preservation of functional vision. The authors have noted no complications that might preclude the use of 103Pd ophthalmic plaque radiotherapy for choroidal melanoma.     

Tumour location affects the incidence of cataract and retinopathy after ophthalmic plaque radiation therapy

AIM: To examine how tumour location affects ocular morbidity after ophthalmic plaque radiotherapy for uveal melanoma. METHODS: 69 eyes were irradiated and followed for a mean 42 months. There were 23 anterior uveal melanomas and 46 were posterior to the equator. Anterior and posterior tumours had similar basal dimensions. Their mean apical heights were 4.8 mm (anterior) and 3.5 mm (posterior) which received a mean 88 Gy and 83.4 Gy respectively. RESULTS: Only one patient (4%) plaqued for an anterior uveal melanoma developed secondary retinopathy (cystoid macular oedema). In contrast, 24 (52%) of the posterior choroidal melanoma patients developed retinopathy (p value <0.0001). Cataract developed in 18 (86%) eyes with phakic anterior tumour compared with seven (17%) eyes with posterior tumours (p value <0.0000). No posterior nasal tumours lost more than two lines of vision though 45% developed retinopathy. CONCLUSION: While plaque radiation of anterior melanomas is more likely to cause reversible vision loss secondary to cataract, treatment of posterior tumours is more likely to be associated with irreversible loss because of retinopathy. Nasal location is also protective against severe loss of vision.     

Cellular radiosensitivity of primary and metastatic human uveal melanoma cell lines

PURPOSE: To investigate the radiosensitivity of uveal melanoma cell lines by a clonogenic survival assay, to improve the efficiency of the radiation regimen. METHODS: Four primary and four metastatic human uveal melanoma cell lines were cultured in the presence of conditioned medium. After single-dose irradiation (0-12 Gy), colonies were allowed to form for 6 to 14 days. Two cutaneous melanomas cell lines were also tested for comparison. The survival curves were analyzed by the linear quadratic (LQ) model, and the surviving fraction at a dose of 2 Gy (SF(2)), the SF at 10 Gy (SF(10)), the ratio of initial irreparably damaged DNA (alpha-coefficient) to the capacity to repair sublethally damaged DNA (beta-coefficient), and the plating efficiency were calculated. RESULTS: The melanomas displayed a wide range of initial irreparable DNA damage (alpha-component), as well as a capacity for repair of sublethal DNA damage (beta-component), which ultimately resulted in a wide range of alpha/beta ratios. These findings were similar in both primary and metastatic melanomas and were comparable with data obtained from two cutaneous melanomas. CONCLUSIONS: Cell lines obtained from primary and metastatic human uveal melanomas displayed a wide range of radiosensitivity, similar to that published for cutaneous melanomas. Translating these data to the clinical setting indicates that a fractionated dose of 8 to 10 Gy administered in three to four fractions, as currently delivered in many centers, should be sufficient to eradicate tumors of approximately 1 cm(3).     

Prospects for radiotherapy of optic nerve meningioma

32 patients with meningioma of the optic nerve, undergone gamma-teletherapy were followed up. The mean total focal dose was 35 Gy. 24 patients were follow-up for 1-8 years. Gamma-, therapy was shown to be the method of choice for treatment of meningiomas in the retrobulbar part of the optic nerve. It permits one to stabilize growth of the tumor, to preserve and, in number of casetelet to elevate the acuity of vision. The decline of acuity of vision was noted only in 3 cases within 6-12 months after the completion of radiotherapy. Even low initial acuity of vision and signs of atrophy of the optic nerve cannot be a ground for pessimistic prediction in relation to the results of treatment.     

Serous detachments of the macula associated with presumed small choroidal melanomas

Eight cases of presumed small choroidal melanomas, associated with subretinal fluid in the macula, were studied to determine the eventual outcome of these tumors and the value of photocoagulation in eliminating subretinal fluid. Photocoagulation resulted in resolution of subretinal fluid involving the macula in six cases for a mean duration of 12 months. Six cases showed tumor growth over a mean interval of 24 months. Two cases were eventually managed with enucleation and two with I125 brachytherapy. The occurrence of subretinal fluid involving the macula in cases of small choroidal melanomas implies a high chance of subsequent tumor growth. Photocoagulation may be useful in eliminating subretinal fluid and improving vision during this observation period.     

Indications and results of operative exposure of traumatically damaged optic nerves (author's transl)]

The indications for operative treatment of traumatically damaged optic nerves are given and the results from microsurgical transethmoid approaches are communicated. This operation method has such a low risk, that it can be also used on patients with recent head injuries. The early diagnosis of traumatic optic nerve damage and the earliest possible exposure of the nerve with pressure relief of the traumatised optic nerves are important for possible success. The development of microsurgery of the orbit, the possibility of a low-risk anaesthetic, the use of modern post-operative therapy and observation make older treatments such as waiting for spontaneous return of vision out of date. During the operation undiagnosed dural tears and other secondary damage are often found, which can be repaired at the same time. This is a further argument for a broadly-based indication to operation.     

经颅视神经减压治疗创伤性视神经损伤12例疗效分析

目的:探讨经颅显微视神经减压术治疗创伤性视神经损伤的疗效及与颅外入路减压术相比之优点。方法:回顾性分析了12例经颅显微视神经管减压手术患者的临床特点和治疗效果,并复习近期颅外入路视神经减压术的相关文献就疗效进行对比。结果:全部患者术后随访3～12mo,手术有效率达83%,无术后脑脊液鼻漏等发生。结论:创伤性视神经损伤的减压手术效果肯定,宜在伤后尽早实施。经颅入路管内段视神经减压术比颅外入路更具优越性,应列为首选。     

Complications of local beta radiation of uveal melanomas

The results of local beta ray radiation of 295 eyes containing a uveal melanoma (including 74 melanomas of the anterior choroid and ciliary body) are presented with special respect to the complications of treatment. The most frequent complications were radiation retinopathy and optic neuropathy. Complications known to occur from other radiation methods, such as dry eye syndrome, loss of cilia, and scleral necrosis, did not occur in our series. The incidence of radiation cataract, as compared to the treatment with⁶⁰Co plaques, was lower in our series. An average of 700 Gy delivered to the scleral base of the tumor was needed for uveal melanomas which could be destroyed. This radiation dose resulted in a 10% incidence of radiation retinopathy.     

Visual outcome after proton beam irradiation of uveal melanoma

Prognostic factors for visual loss following proton irradiation of uveal melanoma were evaluated for 440 eyes treated from 1975 to 1984, with visual acuity 20/200 or better before treatment. Analysis involved Kaplan-Meier survival curves and Cox proportional hazards analysis with visual outcome defined as worse than 20/200. Prognostic factors were tumor height: rate ratio (ratio of rate of visual loss for one category of the variable relative to the rate of visual loss for a reference category of that variable) of 5.26 (95% confidence interval, 2.66-10.39) for tumors greater than 5 mm compared to tumors 3.0 mm or less in height; distance of tumor from the optic disc and fovea: rate ratio 2.59 (1.63-4.11) for tumors 2DD or less from both the optic disc and fovea compared to those greater than 2 DD from these structures. Also predictive of visual loss were tumor location close to disc only, or close to fovea only, macular detachment, worse pretreatment vision, and higher radiation doses delivered to both the disc and fovea, and lens. Regression analysis using a visual acuity scale gave similar results.     

Shot in the dark

A 43-year-old woman presented with decreased vision in the right eye associated with painful eye movements 10 days after receiving her first dose of Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine (Pfizer Inc, New York, NY). Two days later she developed painful loss of vision in the left eye. Clinical presentation and magnetic resonance imaging findings were consistent with bilateral optic perineuritis transitioning to optic neuritis. Extensive evaluation including aquaporin-4 immunoglobin G (IgG), myelin oligodendrocyte glycoprotein IgG, and lumbar puncture was unrevealing. Visual acuity at nadir was counting fingers in both eyes, but after receiving intravenous steroids and plasma exchange vision eventually improved to 20/20 in each eye, although she was left with inferior visual field defects and bilateral optic disc pallor. This case highlights the diagnostic challenge in the evaluation of atypical optic neuritis with a review of post-COVID-19 vaccination-associated optic neuritis.     

视神经外伤经颅视神经管减压术的效果分析

目的分析经颅显微视神经减压术治疗视神经外伤的效果。方法回顾性分析27例经颅显微视神经减压术的手术的时机,效果及影响疗效的相关因素。结果无光感患者13,手术有效率23．1％,视力为光感者11例,有效率63．6％;眼前手动者3例,均有效。总有效率48．1％。无手术并发症。有效患者均为2周内手术病例。结论单纯视神经受压,尚有光感以上视力的患者,早期、充分视神经减压术疗效确切。