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Purpose To provide recommendations for diagnosis of vitreoretinal lymphoma (VRL). Methods Literature was reviewed for reports supporting the diagnosis of VRL. A questionnaire (Delphi 1 round) was distributed to 28 participants. In the second round (Delphi 2), items of the questionnaire not reaching consensus (75% agreement) were discussed to finalize the recommendations. Results Presenting symptoms include floaters and painless loss of vision, vitreous cells organized into sheets or clumps. Retinal lesions are usually multifocal creamy/white in the outer retina. Other findings include retinal lesions with "leopard-skin" appearance and retinal pigment epithelium atrophy. Severe vitreous infiltration without macular edema is the most likely presentation. Diagnostic vitrectomy should be performed. Systemic corticosteroid should be discontinued at least 2 weeks before surgery. An interleukin (IL)-10:IL-6 ratio > 1, positive mutation for the myeloid differentiation primary response 88 gene and monoclonality are indicators of VRL. Multi-modal imaging (optical coherence tomography, fundus autofluorescence) are recommended. Conclusions A consensus meeting allowed the establishment of recommendations important for the diagnosis of VRL.

IMPORTANCE: High-risk histopathologic features of retinoblastoma are useful to assess the risk of systemic metastasis. In this era of globe salvage treatments for retinoblastoma, the definition of high-risk retinoblastoma is evolving. OBJECTIVE: To evaluate variations in the definition of high-risk histopathologic features for metastasis of retinoblastoma in different ocular oncology practices around the world. DESIGN, SETTING, AND PARTICIPANTS: An electronic web-based, nonvalidated 10-question survey was sent in December 2020 to 52 oncologists and pathologists treating retinoblastoma at referral retinoblastoma centers. INTERVENTION: Anonymized survey about the definition of high-risk histopathologic features for metastasis of retinoblastoma. MAIN OUTCOMES AND MEASURES: High-risk histopathologic features that determine further treatment with adjuvant systemic chemotherapy to prevent metastasis. RESULTS: Among the 52 survey recipients, the results are based on the responses from 27 individuals (52%) from 24 different retinoblastoma practices across 16 countries in 6 continents. The following were considered to be high-risk features: postlaminar optic nerve infiltration (27 [100%]), involvement of optic nerve transection (27 [100%]), extrascleral tissue infiltration (27 [100%]), massive (=3 mm) choroidal invasion (25 [93%]), microscopic scleral infiltration (23 [85%]), ciliary body infiltration (20 [74%]), trabecular meshwork invasion (18 [67%]), iris infiltration (17 [63%]), anterior chamber seeds (14 [52%]), laminar optic nerve infiltration (13 [48%]), combination of prelaminar and laminar optic nerve infiltration and minor choroidal invasion (11 [41%]), minor (

SUMMARYRegrasping is a manipulation to alternate between grasp configurations of an object to perform different tasks. We address a regrasping problem termed longitude regrasping to reposition a gripper along an elongated object. We propose an algorithm using the dynamics of the arm and a non-dexterous gripper to perform the manipulation. Energy control is used to toss the object up and catch it under the goal position. Clipped Linear Quadratic Regulator control approach is then applied to the gripper jaws to control the friction force on the object and to let it slide to the final goal position. The object sliding within the gripper is modeled as a semi-active linear joint where only dissipative forces can be applied to it. A set of experiments validated the feasibility of the method.

Vitreo-retinal lymphoma (VRL) is the most common intraocular lymphoma and is highly associated with central nervous system (CNS) lymphoma (CNSL), both posing a therapeutic challenge. We investigated patients' characteristics, efficacy and safety of intravitreal methotrexate (MTX) injections and their outcomes over 20 years. The records of 129 patients diagnosed between 1997 and 2018 were retrospectively reviewed. Lymphoma involved both the CNS and vitreo-retina (49%), solely the CNS (37%) or solely the vitreo-retina (14%). In all, 45·5% of the patients with CNSL either presented with VRL or developed it after a mean (±SE) of 85·7 (7·3) months. In all, 66·0% of the patients diagnosed with VRL either presented with CNSL or developed it after a mean (±SE) 42·6 (7·6) months. The 81 patients with VRL (134 eyes) received a mean (±SD) of 19 (7) injections; however, only 5 (4) injections were needed to reach complete remission. Local recurrence occurred in two of the 81 patients. Overall, 80·2% of eyes had an initial moderate-severe visual loss, and >50% of them improved. Reversible keratopathy was the most prevalent side-effect. A total of 18·5% developed intraocular pressure (IOP) elevation due to angle neovascularisation after 16 injections, which could be reversed with prompt intravitreal injection of bevacizumab. Intravitreal MTX injections are a safe and effective treatment for VRL. Fewer injections (15) may offer similar results with fewer side-effects.

The pathogenesis of ocular surface squamous neoplasia is not fully understood. Therefore, we evaluated the role of oncogenic viruses in the pathogenesis of ocular surface squamous neoplasia in Israel. Patients with ocular surface squamous neoplasia were enrolled in this retrospective study. The specimens were taken during 2004–2015 from two big centers: Emek Medical Center, Afula and the Hadassah Medical Center, Jerusalem. All the specimens (totally 26) were analyzed by immunohistochemistry for evidence of oncogenic viruses that included Human Papilloma virus, Herpes Simplex virus and Cytomegalovirus infection and 14 samples were examined by polymerase chain reaction. In addition, all the samples were examined for Epstein Barr virus infection by immunohistochemistry and Epstein Barr encoding region test. Twenty-six patients were included with a mean age of 61.81 $$\pm$$ 3.83 years (mean $$\pm {\text{SE}})$$ . Immunohistochemistry staining and Epstein Barr encoding region test did not detect any of the oncogenic viruses in the 26 samples. Human Papilloma virus-16 and -18, and Herpes Simplex virus were detected by polymerase chain reaction in 14.2%, 7% and 7%, respectively. We conclude from our study that oncogenic viruses may play a role in the pathogenesis of ocular surface squamous neoplasia in Israel.

Uveal melanoma (UM) is the most frequent intraocular tumor in adult patients. When metastases occur, systemic therapy with alkylating agents (fotemustine or dacarbazine (DTIC)) has shown only modest efficacy. The common chemotherapeutic drug doxorubicin (DOX) is not used to treat metastatic UM (mUM). To expand the chemotherapeutic arsenal for mUM, we tested the effect of DOX on UM cell mortality. We have previously shown that CREB knockdown enhances sensitivity to DOX. UM cells infected with recombinant MuLV-based replicative competent retroviruses (RCR) expressing shRNA targeting CREB were co-treated with either DTIC or DOX. We found that CREB knockdown increases the sensitivity of these cells to both DOX and DTIC in normoxia and more so in hypoxia as measured by cell survival and Caspase 3 activation. The ability to combine CREB knockdown by infection with the RCR recombinant virus which preferentially infects replicating tumor cells and chemotherapy to achieve the same amount of cell death in lower concentrations may result in fewer side effects of the drugs. This combination is a possible new treatment for mUM.

The purpose of this study was to describe the distribution of Muller cell within the peripapillary retinal nerve fiber layer (RNFL) in human eyes. Eleven unpaired normal postmortem eyes were recruited into this study. Each eye was sectioned using the “umbrella technique” to obtain a concentric peripapillary ring centered on the optic disc, with a diameter of 3.0 mm. Immunohistochemistry with anti- CRALBP stained Muller cell within each ring. The RNFL thickness measurements around the peripapillary ring were: 262.5, 339.4, 285.4 and 347.5 μm for the temporal, superior, nasal and inferior quadrants, respectively. Muller cell were found to be unevenly distributed in the peripapillary RNFL of normal eyes. The relative Muller cell staining to the thickness of each measured segment (16.6%, 15.2%, 21.3%, and 17.9% for the temporal, superior, nasal and inferior quadrants, respectively) showed a significant increase in the nasal quadrant. The RNFL thickness measurements obtained using imaging techniques reflect the amount of axonal tissue present in this layer. In this study we highlight that around 20% of RNFL thickness is composed of non-axonal contents which do not represent neuronal tissue, nor are they necessarily lost in the glaucomatous process. More so, the ratio of the Muller cell component to the total RNFL thickness varies around the peripapillary RNFL ring, demonstrating the lowest relative content of Muller cell superiorly and the highest content nasally. Further studies should compare the amount and distribution of Muller cell in normal versus glaucomatous eyes.

Purpose To analyze the accuracy of the Lambda 100 (Heine) potential visual acuity (VA) measurements in subjects undergoing cataract surgery. Methods The medical records of all consecutive patients who underwent clear corneal incision phacoemulsification cataract surgery by a single surgeon between 2010 and 2012 at the Department of Ophthalmology, Hadassah Medical Center, a tertiary care hospital in Jerusalem, Israel, were reviewed. Subjects age 18 or older with a follow-up time of at least 30 days were included. Subjects with previous ocular comorbidities other than glaucoma were excluded. In addition, patients with intraoperative or perioperative complications that could affect final VA were excluded. Analyses were performed to analyze the accuracy of preoperative retinometer potential VA as a predictor of postoperative best-corrected VA. Results A total of 374 operated eyes were included. There was a moderate positive correlation between Lambda estimated VA potential and postoperative achieved best-corrected VA (BCVA) (β coefficient 0.35, pConclusions Lambda may be used to relatively accurately predict postoperative BCVA in cataract patients, specifically in those with moderate cataracts.

Purpose To evaluate the efficacy of the different diagnostic tests for vitreoretinal lymphoma (VRL). Methods A cohort of 150 patients with a presumed diagnosis of VRL. Vitrectomy samples were analysed for cytology, monoclonality [polymerase chain reaction (PCR)] and cytokine levels, and anterior chamber taps were analysed for cytokine levels. Vitreoretinal lymphoma (VRL) was diagnosed after confirming the clinical suspicion with vitreal or brain cytology. Results Vitreoretinal lymphoma (VRL) was diagnosed in 78 patients. Vitreal cytology was positive for 53/132 patients (40.2%), 36/53 had positive cytology from both the eye and the brain. Additional 25 patients had positive brain cytology. Vitreal PCR for monoclonality was positive for 32/91 patients (35.2%). Vitreal cytokine levels of interleukin (IL)-10/IL-6 were >1 for 47/110 patients (43.1%). For cytology, PCR and cytokine analysis, the respective sensitivity was 73.6%, 46.0% and 81.4%, and the accuracy of the tests was 85.6%, 60.4% and 80.9%, respectively. All three tests were available for 79 patients. In this subset, for cytology, PCR and cytokine analysis the respective sensitivity was 79.5%, 41.0% and 82.1%, respectively, and the accuracy of the tests was 89.9%, 60.8% and 81.0%, respectively. Conclusion Cytokines analysis has an important role in the diagnosis of VRL. We suggest analysing cytokines levels in all cases suspected of VRL along with cytology and PCR analysis.

Purpose To collect comprehensive data on choroidal and ciliary body melanoma (CCBM) in children and to validate hypotheses regarding pediatric CCBM: children younger than 18 years, males, and those without ciliary body involvement (CBI) have more favorable survival prognosis than young adults 18 to 24 years of age, females, and those with CBI. Design Retrospective, multicenter observational study. Participants Two hundred ninety-nine patients from 24 ocular oncology centers, of whom 114 were children (median age, 15.1 years; range, 2.7–17.9 years) and 185 were young adults. Methods Data were entered through a secure website and were reviewed centrally. Survival was analyzed using Kaplan-Meier analysis and Cox proportional hazards regression. Main Outcome Measures Proportion of females, tumor-node-metastasis (TNM) stage, cell type, and melanoma-related mortality. Results Cumulative frequency of having CCBM diagnosed increased steadily by 0.8% per year of age between 5 and 10 years of age and, after a 6-year transition period, by 8.8% per year from age 17 years onward. Of children and young adults, 57% and 63% were female, respectively, which exceeded the expected 51% among young adults. Cell type, known for 35% of tumors, and TNM stage (I in 22% and 21%, II in 49% and 52%, III in 30% and 28%, respectively) were comparable for children and young adults. Melanoma-related survival was 97% and 90% at 5 years and 92% and 80% at 10 years for children compared with young adults, respectively ( P = 0.013). Males tended to have a more favorable survival than females among children (100% vs. 85% at 10 years; P = 0.058). Increasing TNM stage was associated with poorer survival (stages I, II, and III: 100% vs. 86% vs. 76%, respectively; P = 0.0011). By multivariate analysis, being a young adult (adjusted hazard rate [HR], 2.57), a higher TNM stage (HR, 2.88 and 8.38 for stages II and III, respectively), and female gender (HR, 2.38) independently predicted less favorable survival. Ciliary body involvement and cell type were not associated with survival. Conclusions This study confirms that children with CCBM have a more favorable survival than young adults 18 to 25 years of age, adjusting for TNM stage and gender. The association between gender and survival varies between age groups.

ObjectiveTo present an established practice protocol for safe and effective hospital-setting ophthalmic practice during the coronavirus disease 2019 (COVID-19) pandemic.Methods and AnalysisLiterature was reviewed to identify articles relevant to COVID-19 pandemic and ophthalmology. The following keywords were used: COVID-19, SARS-CoV-2 and telemedicine, combined with eye, ophthalmology, conjunctivitis and tears. Data were extracted from the identified manuscripts and discussed among subspecialists to obtain consensus evidence-based practice.ResultsA protocol for ophthalmic practice in the era of COVID-19 pandemic was established. The protocol covered patient screening, clinic flow, required personal protective equipment and modifications of ophthalmic equipment for improved safety.ConclusionImportant literature emerged with respect to the practice of ophthalmology in the era of COVID-19. An evidence-based ophthalmic practice protocol was established and should be modified in the future to accommodate new insights on the COVID-19 pandemic.

Background Monocular vision has been found to have a negative effect on children's motion processing and motor functions. Yet, knowledge of motor function of survivors of retinoblastoma (RB) with monocular vision (due to enucleation, for example) is limited. This study examined motor function and its relationship to visual-related and health-related quality of life (HRQOL) in survivors of RB with monocular vision. Procedure Parents of 27 survivors of RB, who underwent an enucleation of one eye resulting in monocular vision, and of 21 typically developing children between the ages of 6 and 12, were administered questionnaires relating to their children's motor function (DCDQ), as well as vision-related function (CVFQ) and HRQOL (PedsQL). Results Of the 27 survivors of RB, 7 (25.6%) were found to have difficulties in motor functions, compared with 1 (4.8%) child in the control group. The difficulties were faced mainly in daily function requiring control during movement, including jumping, running, and ball playing. Additionally, significant correlations were found between motor functions and children's QOL. Finally, survivors of RB with monocular vision were found to have lower QOL, specifically physical- and school-related QOL. Conclusion Survivors of RB who have monocular vision have a higher rate of decreased motor function and lower QOL. These results point to a need for ongoing assessment of survivors of RB to allow timely detection of motor deficits and to institute appropriate therapeutic interventions.

Purpose: To investigate spectral domain-optical coherence tomography (SD-OCT) features of untreated circumscribed choroidal hemangioma (CCH), and the optical density (OD) of the associated subretinal fluid (SRF). Procedures: This international retrospective multicenter study conducted at 5 tertiary retina referral centers included 34 patients with symptomatic CCH imaged on SD-OCT. CCH surface, size, and overlying retinal changes and OD ratio (ODR) were evaluated. Results: The mean ODR of the SRF was 0.808 ± 0.287. Tumor base measured on ultrasound correlated significantly with the ODR (p = 0.012). ODR values in cases of CCH were similar to those of choroidal metastasis, but significantly lower than those of choroidal melanoma (p = 0.006). Thirty-two out of 34 cases (94%) presented with a regular smooth choroidal surface. OCT demonstrated SRF overlying the CCH in 29 eyes (85%). The presence of SRF correlated significantly with a larger basal tumor diameter (p = 0.035). OCT displayed sub- and intraretinal hyperreflective foci, correlating with both larger maximal retinal thickness overlying the tumor (p = 0.031) and the amount of SRF (p = 0.016) in 29 eyes (85%). Conclusion: CCH displays typical findings on SD-OCT. ODR is a new important tool in the differential diagnosis of choroidal tumors and should be considered for enhancing the accuracy of diagnosing CCH. This benefit is especially relevant for cases in which the presentation of CCH is atypical.

Central nervous system acute lymphoblastic leukemia (CNS-ALL) is a major clinical problem. Prophylactic therapy is neurotoxic, and a third of the relapses involve the CNS. Increased expression of interleukin 15 (IL-15) in leukemic blasts is associated with increased risk for CNS-ALL. Using in vivo models for CNS leukemia caused by mouse T-ALL and human xenografts of ALL cells, we demonstrate that expression of IL-15 in leukemic cells is associated with the activation of natural killer (NK) cells. This activation limits the outgrowth of leukemic cells in the periphery, but less in the CNS because NK cells are excluded from the CNS. Depletion of NK cells in NOD/SCID mice enabled combined systemic and CNS leukemia of human pre-B-ALL. The killing of human leukemia lymphoblasts by NK cells depended on the expression of the NKG2D receptor. Analysis of bone marrow (BM) diagnostic samples derived from children with subsequent CNS-ALL revealed a significantly high expression of the NKG2D and NKp44 receptors. We suggest that the CNS may be an immunologic sanctuary protected from NK-cell activity. CNS prophylactic therapy may thus be needed with emerging NK cell-based therapies against hematopoietic malignancies.

A captive female square-lipped rhinoceros born in 1993 had been showing intermittent signs of bilateral conjunctivitis and conjunctival proliferation since 1998. Periodic improvement was noted, especially in winter, but overall the condition had deteriorated over the years. Treatment with various topical, intralesional, and systemic antibiotics and glucocorticosteroids was largely ineffective, as were repeated dewormings. No primary cause for these lesions was found in biopsies taken in 2000 and 2006, although a severe infiltrate of numerous eosinophils was observed in the latter. As the condition worsened, secondary corneal changes were noted, and eventually vision was lost due to proliferative conjunctival tissue. Aggressive resection of the proliferating tissue in 2013 restored vision and submitted biopsies yielded a diagnosis of severe allergic conjunctivitis, eosinophilic granuloma, and habronematid (Habronema or Draschia) larval infection. As no other rhinoceros in the herd was affected, including two calves born to the patient who were in close contact with their mother, it was concluded the presentation was most likely due to a hypersensitivity reaction to the dead or dying larvae. Fly repellent is now regularly applied around the eye of this rhinoceros, and a protective face mask has been fitted. Ongoing periodic relapses are treated with oral ivermectin, topical antibiotics, and steroids.

The goal of this experiment was to evaluate and compare the antimicrobial efficacy of routine preoperative hand washing using commercial medicated sponge brushes versus an alcoholic hand rub, by comparing bacterial growth on ophthalmic surgeons' hands after application of each of these methods.Twenty ophthalmic surgeons were recruited at the Hadassah-Hebrew University Medical Center in Jerusalem, Israel. Samples were collected twice from the hands of each surgeon after hand decontamination using two different protocols during routine surgical practice. The routine preparation consisted of a 3-minute surgical scrub using commercial brush-sponges incorporating either 4% chlorhexidine gluconate (CHG) or 1% povidone-iodine (PVP-I) formulations with detergent, followed by drying the hands with a sterile towel, while the 70% ethanol solution was applied for 60-seconds and allowed to air dry. Half of the group was randomly assigned to provide samples first after the routine method and the alcoholic solution a week later, and the other half of the group was sampled in the reverse order. Viable counts of bacteria were evaluated using a modified glove juice method. Bacterial colonies were enumerated after incubation for 24 hours and expressed as colony forming units (CFU)/mL for each pair of hands.Geometric mean counts were 1310 and 39 CFU/mL, in the routine and alcohol rub groups, respectively, representing a mean logThis study provides evidence that an alcohol rub protocol is more effective in reducing bacterial counts on hands than routine surgical hand preparation with PVP-I and CHG in a population of practicing ophthalmic surgeons in the operative clinical setting. Thus, it provides a safe alternative as a preoperative hand disinfection method.

Purpose Patients with uveal melanoma (UM) undergo lifelong follow-up as metastases can occur more than 20 years after diagnosis. Little is known about the quality of life (QoL) of UM survivors over such an extended period. To investigate their QoL, we used various estimating factors. Methods A cohort of patients diagnosed and treated for UM with regularly scheduled follow-up visits was asked to fill in a European Organization for Research and Treatment of Cancer (EORTC) questionnaire comprised of the EORTC QLQ-C30 and EORTC QLQ-OPT30 modules. An additional open question examined other changes in the patients' lifestyle since diagnosis. Independent demographic and medical data were collected from patient records. Results Two hundred and thirty-two of 294 patients agreed to complete the questionnaire. General QoL correlated highly with the eye-related QoL. Statistically significant higher QoL was associated with tumours not involving the ciliary body, and with better best-corrected visual acuity (BCVA). A subgroup of 39% of the patients reported severe disability affecting eye-related tasks. Thirty-three per cent were highly concerned about various aspects of their future health. Patients who underwent enucleation reported lower eye-related QoL and described problems related to body image in response to the open question. Conclusion General QoL of UM patients is only slightly affected by their malignancy. However, body image and psychosocial adjustment are major issues involved in evaluating QoL. Continuous long-term psychosocial treatment is needed from the time of diagnosis in a subgroup of patients suffering from eye-related disabilities.

Importance The risk of extraocular extension from injecting chemotherapy into eyes with retinoblastoma is minimally understood; however, understanding this risk is important because of the increasing use of intravitreous chemotherapy. Objective To evaluate the risk of extraocular extension in eyes with retinoblastoma that have received intravitreous chemotherapy injections. Design, Setting, and Participants This retrospective cohort study was performed in 655 patients at 10 retinoblastoma centers in North and South American, European, Israeli, and Chinese centers. Physicians at the retinoblastoma centers administered more than 120 intravitreous chemotherapy injections in eyes with retinoblastoma from February 1, 1999, through February 28, 2017. Main Outcomes and Measures Risk of extraocular extension with secondary observational variables, including injection and precautionary techniques. Results A total of 3553 intravitreous chemotherapy injections (3201 melphalan hydrochloride, 335 topotecan hydrochloride, and 17 methotrexate sodium) were administered to 704 eyes in 655 patients with retinoblastoma (mean [SD] age of patients at the time of the initial injections, 31.6 [11.6] months; 348 male [53.1%]). There were no extraocular tumor events related to prior intravitreous injections. This finding resulted in a calculated proportion of zero extraocular events per eye. According to the rule of 3, the risk is no greater than 0.08% injections. All 10 centers included in this study used at least 2 presumed precautionary injection methods (lowering of intraocular pressure, cryotherapy, ocular surface irrigation, ultrasonic biomicroscopy surveillance of the injection site, and subconjunctival chemotherapy deposition). Conclusions and Relevance With use of at least 2 presumed precautionary safety methods, no extraocular extension of tumor events occurred. According to the rule of 3, this finding suggests that the risk is no greater than 0.08% injections.

Uveal melanoma (UM) is the most prevalent primary intraocular cancer in adults. Up to half the patients develop metastases that are currently incurable, and most patients die within two years following the diagnosis of metastases. Therefore, novel therapeutic approaches are required. It has been established that tumor cells are more resistant to the hypoxia cue than non-malignant cells and can remain viable in hypoxia. Oxygen absence in hypoxic tumor areas means the absence of chemotherapeutics and the absence of the effector for radiotherapy (free oxygen radicals). To overcome this treatment resistance, we constructed MuLV-based replication-competent retroviral (RCR) vectors expressing shRNA targeting the hypoxia-response regulating genes CREB and HIF-1. These RCRs express shRNAs either against a single exon or against an exon and the poly-A signal to minimize the point-mutation resistance. These RCRs that only infect replicating cells will preferentially infect tumor cells. Pre-infected Mel270 UM subcutaneous xenografts in SCID mice were monitored weekly in vivo via bioluminescence. Here, we demonstrate that the knockdown of CREB or HIF-1 in UM cells dramatically decreases UM tumor progression. The reduction of the expression of Glut-1, which is a major glucose transporter in cancer cells, within tumors that are infected with the armed viruses may indicate UM&rsquo, s dependence on glycolysis for tumor progression.

Objective To report clinical, histopathological and molecular features of ‘salmon patch’-like conjunctival lesions in paediatric and adolescent patients, and discuss management of these patients and outcome. Methods Patients who presented between 2000 and 2011 with a conjunctival ‘salmon-patch’-like lesion in the plical area, were identified by chart review. Clinical parameters, demographic characteristics and details of ophthalmic imaging were collected, and the effect of treatment examined. Results Eleven patients aged 6–21 years, presented with an elevated pink conjunctival mass in the plical area of one or both eyes. Nine patients underwent an excisional biopsy that histopathologically disclosed extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (also termed ‘MALT lymphoma’) in two cases and reactive lymphoid hyperplasia (RLH) in seven cases. Molecular diagnosis showed polyclonal B cells in six patients, monoclonal B cells in two patients, and a questionable status in one patient. Systemic examination disclosed localised ocular adnexal disease in the patients with MALT lymphoma, and none had either local or systemic recurrence during follow-up. Two other patients were treated with antiallergic medication with resolution of the lesion, and were therefore diagnosed clinically with RLH. Conclusions It is clinically difficult to differentiate between conjunctival RLH and MALT lymphoma in the paediatric and adolescent population. Both lesions are rare in this age group, particularly MALT lymphoma. Molecular analysis of excised lesions does not always correlate with histopathology. A short treatment course with antiallergic drops may sometimes assist diagnosis without compromising the patients due to the indolent nature of lymphoma in that area.

Aims Retinal detachment can develop following brachytherapy for uveal melanoma. This complication may result in substantial visual loss and poses a significant therapeutic dilemma due to the required surgical intervention for correction of the detachment. We report the incidence of retinal detachment in eyes treated with brachytherapy for posterior uveal melanoma and the outcome of pars plana vitrectomy in those eyes. Methods Patients who developed tractional or combined tractional–rhegmatogenous retinal detachment following brachytherapy for posterior uveal melanoma in a single referral centre were retrospectively evaluated. Clinical findings, demographics, and ophthalmic imaging findings were recorded, as well as the manner of treatment and its success. Results Seven of the 473 posterior uveal melanoma patients (1.48%), who were treated between 2000 and 2011 with brachytherapy, developed tractional or combined tractional–rhegmatogenous retinal detachment. Retinal detachment developed at a mean of 50.1 months (range 3.5–120 months) following brachytherapy. All patients underwent pars plana vitrectomy. Retinas remained attached in each of the cases. In five of seven patients there was substantial improvement in visual acuity following repair of the retinal detachment. No tumour growth or dissemination were observed during the mean follow-up of 18.4 months after vitrectomy (range 10–36 months). Conclusions Tractional and tractional–rhegmatogenous retinal detachment are rare complications of treated uveal melanoma. Pars plana vitrectomy appears to be an effective and safe procedure in such cases.

PURPOSE: To compare Orbscan II central corneal thickness (CCT) measurements corrected by five mathematical methods with ultrasound (US) CCT measurements. METHODS: The preoperative CCT examinations of the right eyes of 3242 consecutive candidates for refractive surgery were retrospectively reviewed. Raw Orbscan data were processed by five correction methods: multiplication, subtraction, polynomial, logarithmic, and power. For each correction method, the concordance between corrected Orbscan and US pachymetries was assessed by mean, Pearson correlation, regression analysis, 95% limits of agreement (LoA), and percentage of eyes within 8 μm of US pachymetry. RESULTS: Throughout the 3242 eyes analyzed, we found a high Pearson correlation between Orbscan and US measurements with all correction methods assessed. The linear multiplication and subtraction correction methods brought about mean Orbscan CCT similar to mean US CCT measurements. However, they led to relatively high 95% LoA intervals and low percentage of eyes within 8 μm of US pachymetry. In contrast, the three nonlinear correction methods proposed herein for the first time narrowed the 95% LoA interval (Bland-Altman analysis) together with providing mean Orbscan CCT similar to mean US CCT measurements. Moreover, the power fit was the only method that was reproducible when extracted from one subset of the cohort and applied in another. CONCLUSIONS: Broad 95% LoA intervals were obtained when applying the multiplication and the subtraction correction methods, indicating a poor agreement between the devices. We suggest the power fit as the default method for adjusting Orbscan to US CCT readings.

Aim To evaluate the histopathologic factors statistically associated with the presence of calcification in eyes with retinoblastoma. Methods Retrospective, consecutive and observational case series. Three hundred and two enucleated eyes with retinoblastoma examined between the years 1960 and 2008. Five representative histopathologic slides of the pupil–optic nerve section and three cross optic nerve sections were retrospectively reviewed. The presence and degree of calcification as well as other histopathologic features were evaluated. Demographic data including age, gender and country of origin of the case were also reviewed. Univariate and multivariate statistical analyses were performed to search for a possible correlation between calcification and the other histopathologic factors and/or demographic data. Results Calcification was present in 84.9% of cases. Age, tumour size, necrosis, basophilic staining, iris neovascularisation, choroidal, scleral and/or optic nerve invasion were correlated significantly with calcification. Multivariate analysis showed a significant correlation between the presence of calcification and the amount of necrosis and choroidal invasion only. Conclusions In this series, calcification was more frequent in cases with more necrosis and cases with choroidal invasion, a known poor histopathologic risk factor for metastatic disease. The possible clinical implication of the findings from this study deserves additional studies.

A benign sacrococcygeal teratoma was resected from an infant at birth. Four weeks later, intraocular tumors were identified in the right eye. The eye expanded in size and was removed at 16 weeks. A benign cystic intraocular teratoma was identified.

Aims: Ruthenium-106 brachytherapy is an effective method for treating small to medium uveal melanomas. The purpose of this study was to examine its effectiveness and safety in the management of thick posterior uveal melanoma (apical height ⩾8.0 mm) and to compare it with enucleation. Methods: 126 consecutive patients with thick uveal melanoma were included. 63 patients treated with Ruthenium-106 brachytherapy were compared with 63 patients treated with enucleation. The main outcome measures were visual acuity, eye retention, local recurrence, metastases, all-cause mortality and melanoma-related mortality. Results: Patients treated with brachytherapy were significantly younger and had significantly smaller tumours, compared with patients treated with enucleation. Tumour thickness in the brachytherapy group was 9.3 (SD 0.9) mm compared with 12.2 (1.9) mm in the enucleation group. The 5- and 10-year melanoma-related mortality was 20.5% and 46.2% for brachytherapy patients and 28.1% and 44.0% for enucleation patients (p = 0.6 and p = 0.9). When comparing 15 brachytherapy with 15 matched enucleation patients, the 5-year melanoma-related mortalities were similar, 28.6% and 33.3% respectively (p = 0.7). Complications associated with brachytherapy included tumour regrowth (n = 15), scleral melt (n = 3), neovascular glaucoma (n = 5) and vitreous haemorrhage (n = 3). In the brachytherapy group, no significant difference in survival was noted between patients who did and did not develop local recurrence (p = 0.9). Of the eyes that were initially treated with brachytherapy, 71.4% were saved from enucleation. Of these, 70.8% had a final visual acuity of 20/200 or better. Conclusions: Ruthenium-106 brachytherapy is an alternative to enucleation in some thick posterior uveal melanomas.

Aim: To describe our experience in treating vitreoretinal involvement of primary central nervous system lymphoma, by intravitreal injections of methotrexate (MTX). Methods: Patients with suspected intraocular lymphoma underwent a diagnostic vitrectomy. Samples were sent for cytology, genetic evaluation and for interleukin level measurements. Treatment protocol included injection of 400 μg/0.1 ml MTX intravitreally twice weekly for 4 weeks, once weekly for 8 weeks, and then once monthly for 9 months, for a total of 25 injections. Data were collected from the patients’ records and included, inter alia, response to intravitreal MTX measured by time to disappearance of vitreal cells and retinal infiltrates, changes in visual acuity, and clinical recurrence rate. Results: In the past 10 years we have treated 44 eyes of 26 patients; seven patients had monocular involvement, and 19 binocular. Six patients were initially diagnosed as having a non-responsive uveitis, and 16 with either CNS or systemic lymphoma with later involvement of the eye. Four patients had systemic lymphoma; one of them was found to have CNS lymphoma after the ocular involvement. Three patients had T cell lymphoma, and the rest had B cell lymphoma. Clinical remission was reached after 6.4 (3.4) (2–16) injections of MTX (mean (SD) (range)), with 95% of the eyes needing 13 injections or less to be cleared of malignant cells. None of the patients had an intraocular recurrence. Among the side effects, the most common was corneal epitheliopathy, which usually appeared after the third injection and began to subside when the intervals between injections increased. Conclusions: Vitreoretinal involvement of lymphoma can be controlled effectively and without serious adverse reactions by intravitreal MTX injections. The treatment protocol described herein has resulted in no intraocular recurrence so far and has had bearable side effects. The accumulating clinical results bring us to propose the consideration of this protocol as a good first-line treatment option for intraocular lymphoma.

Vasculogenic mimicry patterns, formed by highly invasive melanoma cells, connect to endothelial cell-lined blood vessels and contain fluid in vitroand in vivo. This study was designed to determine if fluid leaks into vasculogenic mimicry patterns without circulation, or if fluid circulates in and clears from these patterns.Indocyanine green (ICG) laser scanning confocal angiography (Heidelberg Retinal Angiograph (HRA); Heidelberg Engineering, Heidelberg, Germany) was performed on nine patients with posterior choroidal melanoma in an institutional setting. Blood was drawn before the ICG injection and from the contralateral arm of the ICG injection site and 1 min after the injection. Outcome measures include time to first filling of retinal vessels and vasculogenic mimicry patterns and the time at which no fluorescence could be detected by the HRA instrument. After fluorescence was no longer detected in vessels or patterns, the tubes containing the patient's blood was imaged by the Heidelberg HRA.Looping vasculogenic mimicry patterns were detected focally in five patients within 30 s after injection and were detectable up to 12 min post-injection. Blood drawn before ICG injection did not autofluoresce but ICG-containing blood pooled in the tube continued to fluoresce at 1-month post-injection.Vasculogenic mimicry patterns are not part of the endothelial cell-lined vascular system and fluid enters these patterns through leakage. The rapid infusion of ICG into these patterns after injection and the disappearance of fluorescence detectable by the Heidelberg HRA suggest that fluid circulates in these patterns and does not accumulate as a stagnant pool.

Purpose To ascertain operator learning effect, and to quantify the interoperator reproducibility, using the newly introduced GDx VCC (variable corneal compensator) scanning laser polarimeter. Design Prospective instrument validation study. Participants Three operators with no prior experience in operating the GDx VCC examined one randomly chosen eye of each of 30 randomly ordered subjects (15 glaucoma patients and 15 normal subjects). Methods Each study eye was scanned by the 3 operators in a random sequence during a single session. Five GDx parameters were analyzed: TSNIT (temporal, superior, nasal, inferior, temporal) Average, TSNIT Standard Deviation (SD), Superior Average, Inferior Average, and Nerve Fiber Indicator (NFI). Main outcome measures Retinal nerve fiber layer (RNFL) thickness GDx parameters across operators. Results A learning effect was not found for any of the operators for any of the 5 GDx parameters studied. Reproducibility for each GDx parameter was measured as the mean SD value of the measurements taken by the 3 operators. Interoperator reproducibilities for normal and glaucomatous eyes, respectively, were 0.8 and 1.6 μm (TSNIT Average), 1.7 and 2.2 μm (Superior Average), 1.6 and 2.7 μm (Inferior Average), 1.3 and 1.7 μm (TSNIT SD), and 1.4 and 4.6 μm (NFI). The data obtained by each operator were highly correlated with those of the other 2 operators. Conclusions With the commercially available GDx VCC, a learning effect was not found for 3 novice operators. In addition, RNFL measurements seem highly reproducible across operators.

The brain, the testicles, and parts of the eye, including, inter alia, the vitreous, and the retina, are immune-privileged organs with relatively sealed blood-tissue barriers. These three organs may, rarely, develop aggressive primary B-cell lymphoma. Vitreoretinal lymphoma is commonly associated with primary central nervous system lymphoma (PCNSL) and with testicular lymphoma, which has a high incidence of relapse, one of the common sites of relapse is the brain. The association of testicular lymphoma with vitreoretinal lymphoma is extremely rare. In these three organs, in treating the lymphoma, the blood-tissue barrier must be overcome. We present a unique case of a patient with testicular lymphoma who 3 years later was diagnosed with monocular vitreoretinal lymphoma, and while being treated for the ocular lymphoma developed PCNSL. The lymphomas in the three organs were treated successfully: the testicular lymphoma by chemotherapy, rituximab, and radiation therapy, with intrathecal methotrexate (MTX) as a preventative measure; the vitreoretinal lymphoma by intravitreal injections of MTX alone; and the PCNSL by intravenous high-dose MTX, rituximab, dexamethasone, procarbazine, and intrathecal MTX. Ten months after completion of the last treatment, there were no signs of systemic, CNS or ocular recurrence.

A 3-year 10-month-old child initially developed locally recurrent cutaneous eruptions within the first 2 weeks after sustaining a jellyfish sting to her lower extremities. After 5 asymptomatic weeks, she developed unilateral orbital inflammation that did not respond to systemic antibiotics, antihistamines, or steroids. Imaging revealed a rapidly growing mass of the right lacrimal gland. Urgent anterior orbitotomy was performed and the lacrimal gland was biopsied. Histopathologic diagnosis revealed sclerosing dacryodenitis consistent with orbital inflammatory syndrome and/or an immune response to an antigen challenge.

PURPOSE High expression levels of insulin-like growth factor-1 (IGF-1) receptor were associated with metastatic uveal melanoma (UM). The purpose of this study was to examine the potential of serum IGF-1 in early detection of liver metastasis. METHODS IGF-1 serum levels were analyzed using enzyme-linked immunosorbent assay for 118 subjects in three different groups: 55 disease-free (DF) UM patients who did not develop metastasis within 10 years of diagnosis; 22 metastatic patients; and 41 healthy subjects. Matched pairs univariate analysis was performed for sera of 19 metastatic patients 12 and 6 months before the diagnosis of metastasis and on the day of diagnosis, both as time groups and normalized levels per patient. IGF-1 levels were compared among groups by analysis of variance and Student t-test. RESULTS Mean ± SD IGF-1 serum levels for the control, DF, and metastatic groups were 152.48 ± 49.76, 119.92 ± 60.66, and 96.99 ± 56.91 ng/mL, respectively (P < 0.001). Normalized changes in IGF-1 per metastatic patient from 6 months prior to the diagnosis of metastases compared to the day of diagnosis of metastases showed a decreasing trend. CONCLUSIONS IGF-1 levels in 10-years' disease-free UM patients were significantly lower than those in healthy subjects and were even lower in metastatic patients. IGF-1 levels decreased toward the diagnosis of metastases. Therefore, serum IGF-1 level may be used as a predictive biomarker for metastatic UM when measured repeatedly.

Purpose We examined the clinical differences in manifestation and prognosis of uveal melanoma (UM) between men and women. Methods We evaluated 723 UM patients (325 males) who were treated between 1988 and 2010 at a national referral center. Men and women were compared regarding differences in annual distribution, age at diagnosis, size and intraocular location of the tumor, symptoms leading to diagnosis, recurrence, development of metastases, and mortality. Statistical analysis included ANOVA, Pearson correlations, and competing risks for melanoma-related mortality. Results Significant gender differences were not found for annual distribution, diagnosis age, tumor size, or recurrence rate. Tumors were located more frequently posterior to the equator in men than in women. However, men were less likely than women to complain of symptoms before the diagnosis (77.10% vs. 84.65%). Men suffered more metastases. In the subgroup of patients who had metastases, the time until development of metastases was shorter in men (metastases 1 and 5 years after diagnosis of UM: 26% vs. 12.96% and 84% vs. 50%, respectively). The cumulative incidence for melanoma-related mortality was higher for men, with an almost two-fold excess of male melanoma-related mortality in the first 10 years after the diagnosis of UM. Conclusions Men have earlier and more frequent metastases in the first decade after the diagnosis of UM, a fact that may have significant implications in planning clinical trials to test adjuvant therapies to prevent metastasis.

Uveal melanoma (UM) is the most common primary intraocular tumor in adults and is characterized by high rates of metastatic disease. Although brachytherapy is the most common globe-sparing treatment option for small- and medium-sized tumors, the treatment is associated with severe adverse reactions and does not lead to increased survival rates as compared to enucleation. The use of irreversible electroporation (IRE) for tumor ablation has potential advantages in the treatment of tumors in complex organs such as the eye. Following previous theoretical work, herein we evaluate the use of IRE for uveal tumor ablation in human ex vivo eye model. Enucleated eyes of patients with uveal melanoma were treated with short electric pulses (50-100 μs, 1000-2000 V/cm) using a customized electrode design. Tumor bioimpedance was measured before and after treatment and was followed by histopathological evaluation. We found that IRE caused tumor ablation characterized by cell membrane disruption while sparing the non-cellular sclera. Membrane disruption and loss of cellular capacitance were also associated with significant reduction in total tumor impedance and loss of impedance frequency dependence. The effect was more pronounced near the pulsing electrodes and was dependent on time from treatment to fixation. Future studies should further evaluate the potential of IRE as an alternative method of uveal melanoma treatment. © 2013 Mandel et al.

Iris melanomas constitute between 3% and 10% of all malignant melanomas of the uvea and, unlike posterior uveal melanoma, have a low rate of metastasis.1 The most common way of treating circumscribed iris melanoma is by partial, usually sector, iridectomy,2 with iris reconstruction where possible. When the anterior chamber angle or ciliary body is involved, iridotrabeculectomy or iridocyclectomy should be performed. Complications of iridectomy include hyphema, cataract, wound dehiscence, episcleral seeding of the tumour and vitreous loss.1 Non-resectable iris melanoma can be treated by brachytherapy using radioactive plaque3 or proton beam irradiation.4 Diffuse iris melanoma, which often involves the trabecular meshwork and causes secondary glaucoma, is usually treated by enucleation.5 We describe herein a novel technique of sector iridectomy in treating circumscribed iris melanoma. The operation is performed by pushing the tumour out of the eyeball and excising it extraocularly, without intraocular intervention, in order to prevent anterior segment complications. Six patients with growing pigmented iris lesions suspicious for iris melanoma, three of them proven histologically by punch biopsy, underwent resection using this new technique at the Hadassah-Hebrew University Medical Center between 2002 and 2007. All patients signed an informed consent for the described surgery. All …

High levels of serum VEGF have been reported in many types of cancers, especially in the metastatic stage. The aim of this study was to examine the potential of VEGF serum level as a tumor marker for metastases in uveal melanoma (UM) patients.Levels of serum VEGF were analyzed by ELISA for 23 UM patients (none of whom developed metastases within 5 years from diagnosis) at the time of diagnosis, soon after treatment, and 3 years later, and compared with serum VEGF levels of 39 metastatic patients, 58 10-year disease-free (10yDF) patients, and 23 healthy subjects. VEGF ratios were calculated per patient between diagnosis and after treatment, and between diagnosis and 3 years later. Matched pairs univariate analysis was performed for 17 metastatic patients for whom sera were available from before and after the diagnosis of metastases. Patients were followed biannually with liver ultrasonography and liver function tests for the presence of metastases.The inter-patient VEGF level range was large (e.g., the range for the metastatic patients was 46-1892 pg/ml). The mean ± SD levels for the control, 10yDF, and metastatic groups were: 329.65 ± 190.0, 407.66 ± 261.9 and 453.52 ± 270.2, respectively (p = 0.2456). The mean VEGF level ratio from after treatment to diagnosis was 1.08 (p = 0. 0024), and the ratio from 3 years after diagnosis to diagnosis was 1.53 (p = 0.0009). The mean ± SE post/premetastatic levels ratio was 1.35 ± 0.21 (p = 0.0595).Serum VEGF increased significantly after metastases developed. However, the wide inter-patient variance precludes the use of any cut-off level to determine the metastatic status of an individual patient based on a single VEGF serum level. An increase in VEGF on serial measurements may indicate the development of metastases. Further investigation is warranted to assess VEGF's value as a predictive marker for metastatic disease.

Aims: To evaluate the posthepatectomy survival of uveal melanoma patients with liver metastases. Methods: Data were collected from the files in the Departments of Ophthalmology, General Surgery and Oncology, for uveal melanoma patients who were seen in the Ocular Oncology Clinic at the Hadassah Medical Center from 1988 to 2007. The main outcome was posthepatectomy survival. Statistical analysis was performed using JMP statistical software. Results: Of the 558 patients, 74 (13%) developed metastases after a median of 35.0 months from the initial diagnosis. Thirty-five patients underwent hepatectomy. These patients had similar clinical characteristics as those who did not undergo hepatectomy. The median survival time from the detection of metastasis was 3.7-fold higher in the operated patients in comparison with the non-operated patients. Posthepatectomy survival of patients who were found in surgery to have 1–5 metastatic nodules was 3.1 times longer than those with six or more lesions. The hepatectomies of 13 patients resulted in complete resection of the hepatic metastases with clean histological margins (R0). These patients survived 1.9 times longer than those with residual disease (R1/R2). Conclusion: It is possible to extend significantly the life expectancy of uveal melanoma patients who develop isolated hepatic metastases by complete resection of the lesions.

Ocular adnexal lymphoma is a hematopoietic tumor that arises in the conjunctiva, orbit, eyelid, lacrimal gland, or lacrimal sac. The treatment options in children have not been addressed in the literature. The authors describe a 13-year-old child with ocular adnexal lymphoma and discuss the treatment options.

Authentication of cell lines in biomedical research has been elevated to a very high priority. From a review of the literature, Lacroix1 reviewed the issue of cross-contamination of cell lines including the well known contamination of cell lines with HeLa cells,2 and the mis-identification of the ECV304 cell line as “immortalized endothelial cells” when these cells in fact originated from T24 bladder carcinoma cells.3 Lacroix 1 estimated that between 18 and 36% of cell lines have been misclassified. One survey at a large research institution suggested that fewer than 50% of researchers authenticate their cell lines.4 Nardone5 proposed recently that identification of cell lines be required of investigators before grants are awarded, and the National Institutes of Health subsequently called for researchers to authenticate cell lines as a prerequisite for grant funding.6

Aim: To determine the incidence and characteristics of maculopathy associated with blood–brain barrier disruption (BBBD) which is used in treating primary central nervous system lymphoma (PCNSL). Methods: Files of all 56 patients with PCNSL, with or without intraocular lymphoma (IOL), treated at Hadassah University Hospital during the years 1997–2007 were reviewed. Data on 46 patients for whom we had documentation of ocular examination were studied. Those who were alive at the time of the data collection were invited for further evaluation of the presence or absence of maculopathy. The patients were divided into four groups according to treatment protocol. Group 1: systemic intravenous chemotherapy; Group 2: systemic intravenous chemotherapy and intravitreal methotrexate (MTX); Group 3: systemic intra-arterial (IA) chemotherapy and BBBD; Group 4: systemic IA chemotherapy, BBBD, and intravitreal MTX. Results: Of the 23 patients of Groups 1 and 2 who were not treated by BBBD, none developed maculopathy. Of those 23 patients who were treated by BBBD, 12 of 17 (70.5%) in Group 3 and three of six (50%) in Group 4, for a total of 15 of 23 (65.2%) developed maculopathy. The maculopathy did not significantly affect visual acuity in any of them. Conclusions: BBBD may cause maculopathy in almost two-thirds of patients treated for PCNSL, without affecting significantly the visual acuity. Intravitreal injection of MTX, according to the protocol which we apply, is not associated with maculopathy.

Purpose: Vitreoretinal involvement occurs in approximately one-quarter of patients with primary CNS lymphoma (PCNSL), and in some patients with systemic lymphoma who may later develop CNS lymphoma. The traditional method for treating vitreoretinal lymphoma, which is the common type of intraocular lymphoma, is by external beam radiation, or intravenous or intrathecal chemotherapy; however, recurrences are common. We describe our ten years of experience in treating vitreoretinal involvement of PCNSL by intravitreal injections of methotrexate (MTX). Methods: Biopsy-proven vitreoretinal lymphoma has been treated by intravitreal injections of 400 μg/ml methotrexate. According to our protocol, injections are administered twice weekly for 4 weeks, once weekly for 8 weeks, and then once monthly for 9 months for a total of 25 injections. Results: Forty-four eyes of 26 patients have been treated; 7 patients had monocular involvement and 19 binocular. Twenty-three patients had B-cell lymphoma and 3 patients had T-cell lymphoma. In all patients remission of the intraocular lymphoma was achieved after 6.1 + 3.5 injections (range 2 – 16 injections). None of the patients had an intraocular recurrence. Among the side effects, the most common were conjunctival hyperemia and corneal epitheliopathy, which usually subsided when the interval between the injections increased. Conclusions: In our experience, treatment by intravitreal injections of methotrexate provides complete remission of vitreoretinal lymphoma with, so far, no recurrences and with bearable side effects, and can be considered as alternative treatment to radiotherapy and systemic or intrathecal chemotherapy.

Aim: To obtain iris biopsy samples of sufficient quality and quantity for histopathological analysis using a novel punch biopsy technique. Methods: Two patients underwent iris tumour biopsy at an ocular oncology service. A trabeculectomy punch (Kelly Descemet’s membrane punch) with a 1.0 mm diameter head and a 0.75 mm deep bite was inserted through a clear cornea perforated by a SatinSlit 3.2 mm angled slit knife into a viscoelastic-filled anterior chamber. The Kelly punch was placed over the lesion and pressed down before the punch was made. After obtaining the sample, the Kelly punch was removed from the eye and then opened over a dry cellulose sponge. Tissue samples were placed in 4% formalin and processed routinely for standard staining with H&E, periodic acid Schiff and immunostains. Results: In both patients, by using the punch biopsy technique with the Kelly punch, we were able to obtain a 0.8×0.6 mm piece of tissue, large enough for any histological analysis. H&E staining showed spindle cell melanoma. Tissue sections, stained positive with MART-1 (melanoma antigen recognised by T cells) and negative with cytokeratin, established the diagnosis of melanoma of the iris in each of these patients. Conclusions: Iris biopsy with the punch technique yields a tissue biopsy specimen, as opposed to cytology samples obtained by fine needle aspiration biopsy. This technique is quick, simple to perform and requires non-expensive and easily available equipment. The tissue obtained is of sufficient quality and quantity to enable routine and special stainings.

BACKGROUND AND OBJECTIVE The feasibility and reproducibility of scanning laser polarimetry performed through dilated pupils rather than through non-dilated pupils was tested. PATIENTS AND METHODS One eye each of 36 subjects (12 normal, 12 suspected glaucoma, and 12 glaucoma) was scanned using a single GDx unit with variable corneal compensator (GDx-VCC; Laser Diagnostic Technologies, Inc., San Diego, CA). Two scans prior to and two scans after dilation were performed on each study eye, resetting the cornea compensation prior to each scan. The dilated eye was viewed off-center, such that the whitish focusing patch was projected on the 9-o’clock peripheral iris. After adequate anteroposterior focus, the pupil was centered and a scan was acquired. Each of 5 GDx parameters was evaluated comparing the pre-dilation and post-dilation scans. RESULTS No statistically significant difference was found between pre-dilation and post-dilation measurements. There was a high pre-dilation to post-dilation correlation of 98%, 98%, 98%, 93%, and 95% for nerve fiber indicator, TSNIT average, TSNIT standard deviation, superior average, and inferior average, respectively. Less than 5% of the measurement variability was attributed to changes in pupil size (R2 ranging from 0.024 to 0.047). Stratifying the data by diagnostic groups yielded similar results. CONCLUSIONS Pharmacologic mydriasis was not found to influence the retinal nerve fiber layer measurements acquired using the GDx-VCC. Results were comparable to scans achieved in the same eyes prior to dilation. [Ophthalmic Surg Lasers Imaging 2006;37:212-216.] AUTHORS From the Department of Ophthalmology, Hebrew University-Hadassah Medical Center, Jerusalem, Israel. Accepted for publication October 30, 2005. Dr. Blumenthal has received research support from Laser Diagnostic Technologies, Inc., San Diego, CA. Address reprint requests to Eytan Z. Blumenthal, MD, Department of Ophthalmology, Hadassah University Hospital, P. O. Box 12000, Jerusalem 91120, Israel.

Four masked examiners studied the usefulness of the glass-rod for estimating intraocular pressure (IOP) in a living, anesthetized rabbit eye manometrically set to 135 different random values. With training, the average error in IOP estimation improved from 7.42 +/- 5.56 mmHg to 5.13 +/- 4.48 mmHg. Gentle palpation of the corneal apex with a glass-rod provides tactile and visual clues that may assist in estimating the IOP.

PURPOSE: Accurate assessment of the retinal nerve fibre layer (RNFL) is central to the diagnosis and follow-up of glaucoma. The in vivo measurement of RNFL thickness by a variety of digital imaging technologies is becoming an important measure for early detection, as well as for follow-up, of glaucomatous damage. However, when drawing clinical inference concerning the state of the RNFL, it is important to have valid reference data on RNFL thickness in both healthy and diseased eyes. In this review, we summarize the knowledge currently available about RNFL thickness in human and primate eyes. METHODS: A review of the literature on histological analysis of RNFL thickness in the context of glaucomatous damage. CONCLUSIONS: Six studies have so far analysed RNFL thickness. Despite the diverse study methodology taken, a consistent feature of all the data is that the superior and inferior quadrants of the peripapillary retina are thicker than the nasal and temporal quadrants; that the RNFL thickness rapidly diminishes with increasing distance from the disc margin; and that apparently at different locations the ratio of axons to supportive tissue varies significantly. We conclude that limited data are available to describe the normal variation in RNFL thickness in the normal human eye. Further studies may help better characterize the RNFL thickness in health and disease and to facilitate the correlation with clinical methods for nerve fibre layer assessment.

Purpose: To evaluate the presence, duration and magnitude of a learning effect in serial visual field (VF) testing, using the commercially available frequency doubling technology (FDT) instrument. Patients and Methods: 21 healthy adults with no prior VF experience underwent 6 serial VF tests, using the full-threshold C-20 program of the Zeiss-Humphrey FDT analyzer, on one randomly chosen eye. Tests were spaced at least two days apart. Results: The average mean sensitivity was 32.37 ± 2.6 dB; the average mean deviation (MD) was 1.22 ± 1.8 dB. The MD at the first examination (0.28 ± 2.1 dB) was significantly poorer than at any of the other testing sessions (p

We thank Dr Chia Seen Nee for the interest in our research.1 As Dr Chia Seen Nee have described,2 the cases which are presented in our manuscript demonstrate retinal detachment that …

PURPOSE: To develop a method to screen for serum biomarkers of early hepatic metastasis from uveal melanoma. METHODS: Cytokeratin 18 (TPS) was identified from gene expression profiles as protein generated by highly invasive uveal melanoma cells. Sera were collected from two groups of 15 SCID mice 2 weeks after injection of either tissue culture medium or MUM2B human metastatic uveal melanoma cells into the mouse liver. Serum TPS levels were assayed in 53 healthy human controls, 64 uveal melanoma patients who were disease free for at least 10 years, and 37 patients with metastatic uveal melanoma. RESULTS: After 2 weeks, small hepatic nodules (0.1-2.8 mm; mean, 0.80 mm) developed in 11 of 15 mice injected with MUM2B cells. Serum TPS levels in media-injected mice (84.7 U/L) were substantially lower than levels in MUM2B-injected mice (601 mug/L). TPS levels were significantly higher (P < 0.0001) in patients with metastatic uveal melanoma (139.63 +/- 22.20) than in healthy controls (54.23 +/- 0.01) or in patients free of disease (69.29 +/- 9.76). Significant differences were found between TPS levels before and after the development of hepatic metastases (P < 0.01), and serum TPS levels became elevated in four patients at least 6 months before the detection of hepatic metastases by abdominal ultrasonography. CONCLUSIONS: The direct-injection model of uveal melanoma in the mouse liver may be used to screen for potential serum biomarkers of metastatic uveal melanoma.