Feasibility of Proton Beam Therapy for Ocular Melanoma Using a Novel 3D Treatment Planning Technique.

PURPOSE: We evaluated sparing of normal structures using 3-dimensional (3D) treatment planning for proton therapy of ocular melanomas. METHODS AND MATERIALS: We evaluated 26 consecutive patients with choroidal melanomas on a prospective registry. Ophthalmologic work-up included fundoscopic photographs, fluorescein angiography, ultrasonographic evaluation of tumor dimensions, and magnetic resonance imaging of orbits. Three tantalum clips were placed as fiducial markers to confirm eye position for treatment. Macula, fovea, optic disc, optic nerve, ciliary body, lacrimal gland, lens, and gross tumor volume were contoured on treatment planning compute tomography scans. 3D treatment planning was performed using noncoplanar field arrangements. Patients were typically treated with 3 fields, with at least 95% of planning target volume receiving 50 GyRBE in 5 fractions. RESULTS: Tumor stage was T1a in 10 patients, T2a in 10 patients, T2b in 1 patient, T3a in 2 patients, T3b in 1 patient, and T4a in 2 patients. Acute toxicity was mild. All patients completed treatment as planned. Mean optic nerve dose was 10.1 Gy relative biological effectiveness (RBE). Ciliary body doses were higher for nasal (mean: 11.4 GyRBE) than temporal tumors (5.8 GyRBE). Median follow-up was 31 months (range: 18-40 months). Six patients developed changes which required intraocular bevacizumab or corticosteroid therapy, but only 1 patient developed neovascular glaucoma. Five patients have since died: 1 from metastatic disease and 4 from other causes. Two patients have since required enucleation: 1 due to tumor and 1 due to neovascular glaucoma. CONCLUSIONS: 3D treatment planning can be used to obtain appropriate coverage of choroidal melanomas. This technique is feasible with relatively low doses to anterior structures, and appears to have acceptable rates of local control with low risk of enucleation. Further evaluation and follow-up is needed to determine optimal dose-volume relationships for organs at risk to decrease complications rates.

Outer retinal structure after closed-globe blunt ocular trauma.

PURPOSE: To evaluate outer retinal structural abnormalities in patients with visual deficits after closed-globe blunt ocular trauma. METHODS: Nine subjects with visual complaints after closed-globe blunt ocular trauma were examined between 1 month after trauma and 6 years after trauma. Spectral domain optical coherence tomography was used to assess the outer retinal architecture, whereas adaptive optics scanning light ophthalmoscopy was used to analyze the photoreceptor mosaic integrity. RESULTS: Visual deficits ranged from central scotomas to decreased visual acuity. Spectral domain optical coherence tomography defects included focal foveal photoreceptor lesions, variable attenuation of the interdigitation zone, and mottling of the outer segment band, with one subject having normal outer retinal structure. Adaptive optics scanning light ophthalmoscopy revealed disruption of the photoreceptor mosaic in all subjects, variably manifesting as foveal focal discontinuities, perifoveal hyporeflective cones, and paracentral regions of selective cone loss. CONCLUSION: We observe persistent outer retinal disruption in subjects with visual complaints after closed-globe blunt ocular trauma, albeit to a variable degree. Adaptive optics scanning light ophthalmoscopy imaging allows the assessment of photoreceptor structure at a level of detail not resolvable using spectral domain optical coherence tomography or other current clinical imaging tools. Multimodal imaging seems to be useful in revealing the cause of visual complaints in patients after closed-globe blunt ocular trauma. Future studies are needed to better understand how photoreceptor structure changes longitudinally in response to various traumas.

Reactivation of retinopathy of prematurity after bevacizumab injection.

OBJECTIVE: To report late reactivation and progression of retinopathy of prematurity (ROP) after intravitreal bevacizumab monotherapy. METHODS: Retrospective review of 9 patients (17 eyes) with recurrence of ROP after initial treatment with intravitreal bevacizumab monotherapy. Data collected included (1) location and stage of ROP activity, (2) number and timing of treatments, and (3) structural outcomes. RESULTS: Mean age at treatment-requiring recurrence was 49.3 weeks (SD, 9.1 weeks; minimum, 37 weeks; maximum, 69 weeks) postmenstrual age (PMA). The mean time between initial treatment and treatment-requiring recurrence was 14.4 weeks, with a minimum of 4 and maximum of 35 weeks. Fives eyes progressed to retinal detachment (4 eyes stage 5, 1 eye stage 4a). Age at retinal detachment ranged from 49 to 69 weeks PMA with a median of 55 weeks PMA and mean of 58.4 weeks PMA. No eye that received laser treatment for recurrence progressed to retinal detachment. CONCLUSIONS: Although intravitreal bevacizumab treatment is effective in inducing regression of ROP, the effect may be transient. Recurrence can occur later in the course than with conventional laser therapy. Late retinal detachment can occur despite early regression. Longterm favorable structural outcome may require extended observation and retreatment. Laser may be a useful treatment for recurrences.

Amiodarone-associated optic neuropathy: a critical review.

Although amiodarone is the most commonly prescribed anti-arrhythmic drug, its use is limited by serious toxicities, including optic neuropathy. Current reports of amiodarone-associated optic neuropathy identified from the Food and Drug Administration's Adverse Event Reporting System and published case reports were reviewed. A total of 296 reports were identified: 214 from the Adverse Event Reporting System, 59 from published case reports, and 23 from adverse events reports for patients enrolled in clinical trials. Mean duration of amiodarone therapy before vision loss was 9 months (range 1-84 months). Insidious onset of amiodarone-associated optic neuropathy (44%) was the most common presentation, and nearly one third were asymptomatic. Optic disk edema was present in 85% of cases. Following drug cessation, 58% had improved visual acuity, 21% were unchanged, and 21% had further decreased visual acuity. Legal blindness (<20/200) was noted in at least one eye in 20% of cases. Close ophthalmologic surveillance of patients during the tenure of amiodarone administration is warranted.

Transconjunctival 20-gauge vitrectomy outcomes.

BACKGROUND AND OBJECTIVE: To investigate the short-term complication profile of the transconjunctival 20-gauge trocar-cannula (20g-TCV) system. PATIENTS AND METHODS: Patients who underwent primary 20g-TCV without history of prior vitrectomy were included. The primary outcome was incidence of short-term hypotony. Other data collected included visual acuity (VA), rate of sclerotomy suture placement, and intraoperative and postoperative complications. RESULTS: One hundred twenty-seven eyes of 120 patients were included. Postoperative complications included hypotony in 10.2% of eyes at the first postoperative day and 4.7% at week 1, all with spontaneous resolution. No cases of endophthalmitis were observed. Overall mean VA significantly improved from 20/375 preoperatively to 20/221 at month 3. CONCLUSION: Although the rate of short-term hypotony was relatively high, it was transient. This 20g-TCV system does not appear to be associated with other intraoperative or postoperative complications. The authors recommend a low threshold for sclerotomy suture placement if adopting this system.

Treating uveitis-associated hypotony with pars plana vitrectomy and silicone oil injection.

PURPOSE: The purpose of this study was to determine the effect on intraocular pressure (IOP) and visual acuity of treating uveitis-related hypotony in patients with vitrectomy and intravitreal silicone oil injection. METHODS: Patients who underwent pars plana vitrectomy and silicone oil injection for uveitis-associated hypotony treatment were identified retrospectively. The primary outcome was maintaining an IOP of > or =5 mmHg. Visual acuity improvement was defined as an increase in > or =2 lines of acuity. RESULTS: Twelve eyes of 10 patients were identified. Median preoperative IOP was 2 mmHg (range: 0-7 mmHg). Two of 12 eyes had an IOP of > or =5 mmHg at presentation. The number of eyes with an IOP of > or =5 mmHg was 7 of 12 eyes (58%) at 1 month, 4 of 12 eyes (33%) at 3 months, 6 of 12 eyes (50%) at 6 months, and 3 of 9 eyes (33%) at 1 year. Five of 12 eyes (42%) were reinjected between 1 and 3 times with silicone oil for recurring hypotony. Median presenting Snellen visual acuity was counting fingers (range: 20/125 to light perception). Seven of 9 eyes (78%) maintained their preoperative vision at 1 year. CONCLUSION: Intraocular pressure elevated modestly in most patients in this series. However, results were often transient, and some eyes required repeated silicone oil injections. Although silicone oil is reasonable to consider for the treatment and maintenance of IOP in patients with ocular hypotony secondary to uveitis, better treatments are needed.

Mucormycosis infection of the lacrimal sac.

Biopsy of the lacrimal sac for patients with primary acquired nasolacrimal duct obstruction has been a topic of debate for many years. The authors present a case of a 72-year-old immunocompetent woman with a 2-month history of epiphora secondary to nasolacrimal duct obstruction. During an uneventful dacryorhinocystostomy, a routine lacrimal sac biopsy was performed and revealed mucormycosis. After appropriate infectious disease consultation, intensive antifungal therapy was given uneventfully. The patient has not had any signs of active Mucor infection after treatment in 6 months of follow up. This case demonstrates the utility of routine lacrimal sac biopsy and stands as an example of the potential to miss a serious diagnosis.

Septo-optic dysplasia with bilateral congenital corneal anesthesia.

Septo-optic dysplasia, or de Morsier syndrome, is characterized by optic nerve hypoplasia with an absent septum pellucidum and/or pituitary abnormalities. Congenital corneal anesthesia is a rare disorder that has been associated with many neurological disorders. Here we present a patient with both conditions who was successfully treated with permanent lateral tarsorrhaphy and aggressive lubrication. To our knowledge, congenital corneal anesthesia has not been reported in association with septo-optic dysplasia. The purpose of this report is to make pediatric ophthalmologists aware of a potential association since the diagnosis of congenital corneal anesthesia is often difficult and delayed.

Intravitreal bevacizumab for neovascular glaucoma.

PURPOSE: To report 6-month and 1 year outcomes of eyes treated for neovascular glaucoma (NVG) with intravitreal bevacizumab injection and panretinal laser (PRP) compared to those receiving PRP alone. DESIGN: retrospective, consecutive case series. METHODS: Charts of patients with NVG from retinal ischemia and at least 6 months of follow-up were reviewed. Patients were treated with one injection of 1.25 mg intravitreal bevacizumab followed by PRP or with PRP alone. The primary outcome was the long-term angle anatomy. Secondary measures included intraocular pressure (IOP), visual acuity, patient compliance, and control of systemic diseases. RESULTS: Fourteen eyes of 12 patients treated with bevacizumab and PRP and 15 eyes of 11 patients treated with PRP alone were included in the study. Mean sectors of open angle at baseline was 1.31 in the bevacizumab group and 1.47 in the retinal ablation group (P = 0.73). Mean sectors of open angle was 2.14 and 1.18 in the bevacizumab and retinal ablation groups, respectively (P < 0.05) at 6-month follow-up, and 2.27 and 1.18, respectively (P < 0.05) at 1-year follow-up. Mean baseline IOP was 32.3 mmHg (+/-14.8) in the bevacizumab group and 31.8 mmHg (+/-13) in the PRP group (P = 0.75). At 6-month follow-up, the mean IOP was 18.28 mmHg (+/-10) in the bevacizumab group and 23.33 mmHg (+/-14.6) in the PRP group (P = 0.05), and 19.12 mmHg (+/-6.8) and 26.2 mmHg (+/-18) (P = 0.1), respectively at 1-year follow-up. Nineteen patients were judged to be noncompliant, 10 had uncontrolled diabetes and 7 had uncontrolled hypertension. CONCLUSIONS: This study documents better long-term preservation of open angle and IOP control in eyes receiving bevacizumab along with PRP. We stress that NVG is still associated with poor visual acuity outcomes.

MRI of orbital cellulitis and orbital abscess: the role of diffusion-weighted imaging.

OBJECTIVE: Our aims were to describe the role of diffusion-weighted imaging (DWI) in detecting abscess as a complication of orbital cellulitis and to assess whether abscess can be diagnosed with a combination of conventional unenhanced sequences and whole-brain DWI with parallel acquisition. Nine cases of orbital cellulitis imaged with MRI were retrospectively reviewed, including six cases with pyogenic abscess. CONCLUSION: In this preliminary study, DWI improved diagnostic confidence in nearly all cases of orbital abscess when used in conjunction with contrast-enhanced imaging. DWI also confirmed abscess in a majority of cases without contrast-enhanced imaging, which may be of particular use when contrast material is contraindicated.

Flecked-retina syndromes.

A number of retinal disorders may present with fleck-like lesions in the retina. We describe the case of a 13-year-old girl who presented with a complaint of decreased vision and prior diagnosis of "fleck-retina." Further examination revealed that the patient had an autosomal recessive disorder associated with systemic manifestations. In the current article, the authors describe the case report and briefly review the various autosomal-recessive disorders that may present with "retinal flecks."

Objective measurement of periocular pigmentation.

PURPOSE: To evaluate the Minolta CR-400 chromameter in objectively measuring periocular/facial pigmentation in subjects of different ethnicities. METHODS: The CR-400 was used to obtain skin color measurements from 75 African-American, Caucasian and Hispanic subjects in 16 facial and periocular locations. Comparisons between ethnic and Fitzpatrick groups and instrument reliability were analyzed. RESULTS: Significant differences in L* were observed among all three ethnic groups, while values a* and b* were less sensitive to differences in pigmentation. Comparison between Fitzpatrick groups again identified value L* as being the most sensitive, demonstrating significant differences between the more heavily pigmented groups. The 16 facial locations measured were found to be statistically similar to each other, and the chromameter demonstrated excellent inter- and intra-instrument reliability. CONCLUSIONS: The Minolta CR-400 chromameter reliably measures facial pigmentation and can be useful for studies evaluating changes in skin pigmentation. Value L* is the parameter that is most sensitive to differences between ethnic and Fitzpatrick groups. Overlap between groups was observed, demonstrating that in future studies, each individual must serve as their own control when monitoring changes in pigmentation. The similarity between all the locations tested demonstrates uniformity of facial pigmentation within an individual.

Corneal pathology in microphthalmia with linear skin defects syndrome.

PURPOSE: To describe the histopathology of the cornea in microphthalmia with linear streaks (MLS) syndrome. METHODS: Two patients with MLS syndrome underwent penetrating keratoplasty. This study describes the histopathology and investigates immunophenotype of the corneal extracellular matrix by using keratan sulfate and collagen type III antibodies. RESULTS: Clinical examination revealed bilateral sclerocornea and characteristic skin changes. By light microscopy, central corneal stroma in both patients showed vascularization and irregular thick collagen lamellae typical of sclerocornea. In addition, corneal thinning, anterior synechiae, and the absence of the Descemet membrane were noted, which was suggestive of Peters anomaly. Diffuse and intense anti-keratan sulfate staining and minimal anti-collagen type III stromal staining were seen in both corneal buttons. CONCLUSIONS: The cornea in MLS may clinically resemble sclerocornea. Histologic features resemble those previously described in sclerocornea and also seen in anterior segment dysgeneses. Keratan sulfate and collagen type III labeling suggests that the corneal extracellular matrix resembled cornea and not sclera.

Histologic findings after surgical excision of optic nerve head drusen.

PURPOSE: To report the histopathologic findings of a case of bilateral massive optic nerve head (ONH) drusen. METHODS: A 59-year-old man presented with bilateral massive ONH drusen and secondary compromise of the retinal vasculature leading to vision of counting fingers at 1 ft in the left eye and 20/30 in the right eye. The inferior one half of the left ONH druse was excised resulting in no light perception vision postoperatively. RESULTS: Energy-dispersive spectroscopy suggested the composition of the ONH druse to be calcium phosphate (Ca3[PO4]2), which has implications on pathogenesis of neuronal cell death in ONH drusen. Scanning electron microscopy demonstrated embedded metal particles, likely to be remnants of the instruments used. CONCLUSION: Massive ONH drusen are actually one large druse that has multiple excrescences on its surface giving it the variegated appearance. Although surgical excision of ONH drusen may be technically possible, consideration should be given to improvements in instrumentation and patient selection criteria.

Deep lamellar endothelial keratoplasty: histopathology of complications in initial cases.

PURPOSE: To report complications encountered after 2 initial cases of deep lamellar endothelial keratoplasty. METHODS: Review of clinical findings of 2 initial cases in which intraoperative and postoperative complications were encountered. Corneal buttons from the 2 cases were evaluated by light microscopy and transmission electron microscopy. RESULTS: Complications encountered were related to the graft-recipient interface and the lamellar dissection of the recipient and donor corneas. CONCLUSION: Deep lamellar endothelial keratoplasty is an evolving procedure that shows much promise. These 2 cases show that the procedure entails a separate skill set from penetrating keratoplasty and requires significant surgeon practice before being introduced into the individual's transplant practice.

The effect of temperature on the antimicrobial activity of Optisol-GS.

PURPOSE: To determine the survival of different bacteria inoculated in Optisol-GS at refrigerated storage temperature (6 degrees C) and after subsequent warming to room temperature (19-22 degrees C). METHODS: Staphylococcus aureus, Enterococcus faecium, Streptococcus pneumoniae, and Pseudomonas aeruginosa were chosen from stock clinical isolates for inclusion in the study. The first group consisted of 12 Optisol-GS vials. The second group consisted of 12 Optisol-GS vials containing corneas inappropriate for transplantation according to the Eye Bank Association of America (EBAA) protocols. Each group was inoculated with 3 concentrations of approximately 10, 10, and 10 colony-forming units (CFU)/mL of each bacterial species and then refrigerated per EBAA protocol. After 48 hours of refrigeration, all vials were placed at room temperature (RT) and counts were performed at 48, 50 (2 hour RT), 54 (6 hour RT), 60 (12 hour RT), 72 (24 hour RT), and 96 (48 hour RT) hours. At 96 hours, the corneal tissue from 10 and 10 inocula were cultured. All samples underwent serial dilution, spiral plating on blood agar plates, and incubation at 35 degrees C. Viable colony counts were determined at 24 hours. RESULTS: Except for the 10 CFU/mL inocula of P. aeruginosa, all isolates were viable after 48 hours of refrigeration. Rapid bactericidal activity was observed against P. aeruginosa after 2 hours at RT, with complete sterilization by 6 hours. The rate and extent of killing against S. aureus were influenced by the initial inoculum. Bactericidal activity was achieved after 2 hours at RT with 10 CFU/mL of S. aureus versus 24 hours with the 10 inoculum. Of note, bactericidal activity was not observed against S. pneumoniae and E. faecium following 24 hours of storage at RT. The presence of corneal tissue did not affect viable counts, with counts from corneal tissue cultures reflecting the counts seen from Optisol-GS after 48 hours at RT. CONCLUSIONS: The antimicrobial activity of Optisol-GS was reduced at refrigerated temperature and enhanced at RT. Bactericidal activity was not observed against E. faecium at either refrigerated temperature or RT.

Bimatoprost-induced periocular skin hyperpigmentation: histopathological study.

OBJECTIVE: To investigate light microscopic and ultrastructural changes in bimatoprost-induced skin hyperpigmentation. METHODS: Eyelid biopsy specimens from bimatoprost-treated patients and matched controls were examined by light microscopy and transmission electron microscopy. Using an image analyzer, melanin granules were counted on Fontana-Masson-stained sections, and melanosomes were counted on electron micrographs. Immunohistochemical analysis was performed with antibodies against S100 and CD3. Positively labeled cells were counted. RESULTS: By light microscopy, a marked increase in the number of melanin granules was noted in the bimatoprost-treated specimens. Electron microscopy demonstrated dermal melanocytes with prominent rough endoplasmic reticulum and abundant normal-sized melanosomes in different stages of maturation as compared with control specimens. Furthermore, the keratinocytes of the bimatoprost-treated specimens showed abundant mature melanosomes when compared with controls. Also of note, atypical melanocytes were absent in both specimens. The S100-positive melanocytes were comparable in bimatoprost-treated and control specimens. Few CD3- and CD68-positive cells in the bimatoprost-treated specimens were noted in both groups. CONCLUSION: Bimatoprost-induced periocular hyperpigmentation is caused by increased melanogenesis. There was no evidence of melanocyte proliferation or prostaglandin-induced inflammation in the specimens that were examined.

Medulloepithelioma of the ciliary body and optic nerve: clinicopathologic, CT, and MR imaging features.

The definitive diagnosis of medulloepitheliomas of the ciliary body and optic nerve is made by histopathologic examination. Familiarity with rare tumors aids clinicians in accurately diagnosing this rare neoplasm. CT and MR imaging findings can be helpful, especially if the mass is confined in an area of the ciliary body without involvement of the retina. The characteristic findings of cystic changes and possible calcification are suggestive of medulloepithelioma rather than melanoma. The more common and ominous retinoblastoma shares some radiologic features with medulloepithelioma, however, and is thus often a consideration. Clinical diagnosis of medulloepitheliomas of the optic nerve and central nervous system (CNS) is more challenging. The diagnosis is often made by histopathologic examination. Lastly, coexisting CNS tumors and anomalies have been reported in association with intraocular medulloepitheliomas and should be recognized.