Vitreoretinal lymphoma: Central nervous system lymphoma risk with unilateral or bilateral ocular tumour. A multicentre collaboration.

OBJECTIVES: To investigate the risk of developing central nervous system (CNS) lymphoma in patients with vitreoretinal lymphoma (VRL) presenting with unilateral versus (vs.) bilateral ocular involvement. METHODS: Retrospective, multicentre cohort study from January 1, 1984 to December 31, 2020. RESULTS: There were 218 eyes of 127 patients with isolated VRL of the confirmed or presumed diffuse large B-cell subtype in the absence of known CNS or systemic lymphoma. Overall, mean patient age at presentation was 67 years (median 68, range 22-93 years), with 52 (40%) male, and 118 (90%) Caucasian. By univariate Cox regression analysis, two factors were predictive of decreased risk for development of CNS lymphoma, including initial presentation with unilateral VRL (versus bilateral VRL) (HR 0.5 [0.2-0.9], p = 0.02) and use of systemic chemotherapy for initial treatment of isolated ocular disease (HR 0.2 [0.1-0.6], p = 0.002). Both factors remained significant on multivariate and competing risk analyses. Progression from unilateral to bilateral VRL, patient age at presentation, and ocular structures involved (vitreous, subretinal space, subretinal pigment epithelial space) were not significantly associated with CNS lymphoma risk. CONCLUSION: Initial presentation with unilateral VRL and treatment of isolated VRL with systemic chemotherapy were associated with lower risk of developing CNS lymphoma. Further study is required to determine whether select patients with isolated VRL might benefit from systemic chemotherapy in the prevention of CNS lymphoma.

Real-world experience with belantamab mafodotin therapy for relapsed/refractory multiple myeloma: A multicentre retrospective study.

Belantamab mafodotin, an immuno-conjugate targeting B-cell maturation antigen, showed single-agent activity in phase 1 and 2 studies, and was recently approved for heavily pretreated relapsed/refractory multiple myeloma (RRMM) patients. Real-world data and long-term follow-up are scarce. We conducted a multisite retrospective study aimed to assess safety and efficacy of belantamab mafodotin monotherapy administered via the GSK expanded access compassionate care programme. One-hundred and six RRMM patients were treated with belantamab mafodotin between July 2019 and March 2021. The median age was 69.4 years. Patients were heavily pretreated with a median of six (range 2-11) prior therapy lines. Major adverse effects included ocular toxicity (keratopathy 68.4%, grade ≥3: 40.5%; blurred vision 36.8%, grade ≥3: 6.3%), thrombocytopenia (27.4%, grade ≥3: 17.9%) and infections (11.3%, grade ≥3: 7.5%). Median follow-up time was 11.9 [95% confidence interval (CI) 10.0-13.8] months. Overall response rate was 45.5%. Median progression-free survival was 4.7 (95% CI 3.5-5.9) months in the entire cohort and 8.8 (95% CI 6.6-10.9) months among responders. Median overall survival was 14.5 (95% CI 9.5-19.6) months, and not reached for responders. To conclude, in a real-world setting, belantamab mafodotin monotherapy showed efficacy comparable with the prospective clinical trials, with a tolerable toxicity profile.

Orbital nodular fasciitis in child with biallelic germline RBL2 variant.

RBL2/p130 is one of three highly conserved members of the retinoblastoma (RB) protein family. It is strongly upregulated during neuronal differentiation and brain development, and is critical for survival of post-mitotic neurons. Similar to RB1, it has been implicated as a tumor suppressor gene and has been shown to be dysregulated in various types of cancer. Recent publications describe biallelic, germline loss of function variants in RBL2 in individuals with profound developmental delay. We report a child with profound developmental delay, microcephaly, and hypotonia, who developed fulminant exophthalmos at age 6 years. Brain MRI followed by a biopsy of an intra-orbital mass revealed a mesenchymal tumor. Post-surgical histopathologic examination of the resected tumor was compatible with diagnosis of nodular fasciitis. Exome sequencing from peripheral blood identified a biallelic frameshift variant (c.901dupT) in RBL2. Notably, no malignancies were reported in previous cases with RBL2 variants. This case provides a possible association between RBL2 and orbital tumors.

Defining High-risk Retinoblastoma: A Multicenter Global Survey.

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 (<3 mm) choroidal invasion (5 [19%]), and prelaminar optic nerve infiltration (2 [7%]). The other histopathologic features considered high risk included Schlemm canal invasion (4 [15%]) and severe anaplasia (1 [4%]). Four respondents (15%) said that the presence of more than 1 high-risk feature, especially a combination of massive peripapillary choroidal invasion and postlaminar optic nerve infiltration, should be considered very high risk for metastasis. CONCLUSIONS AND RELEVANCE: Responses to this nonvalidated survey conducted in 2020-2021 showed little uniformity in the definition of high-risk retinoblastoma. Postlaminar optic nerve infiltration, involvement of optic nerve transection, and extrascleral tumor extension were the only features uniformly considered as high risk for metastasis across all oncology practices. These findings suggest that the relevance about their value in the current scenario with advanced disease being treated conservatively needs further evaluation; there is also a need to arrive at consensus definitions and conduct prospective multicenter studies to understand their relevance.

Role of oncogenic viruses in the development ocular surface squamous neoplasia.

PURPOSE: 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. METHODS: 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. RESULTS: Twenty-six patients were included with a mean age of 61.81 [Formula: see text] 3.83 years (mean [Formula: see text]. 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. CONCLUSION: We conclude from our study that oncogenic viruses may play a role in the pathogenesis of ocular surface squamous neoplasia in Israel.

Consensus Recommendations for the Diagnosis of Vitreoretinal Lymphoma.

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.

Efficacy and safety of intravitreal methotrexate for vitreo-retinal lymphoma - 20 years of experience.

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 "Crab" Memory Tool for the Actions of the Extraocular Muscles.

INTRODUCTION: Understanding the primary, secondary and tertiary actions of the vertical recti and oblique muscles is important in the diagnosis of various types of strabismus (superior oblique palsy, A- and V-patterns). Unfortunately, learning these actions can be very challenging. We designed a visual memory tool, and assessed its usefulness for medical students. METHODS: Medical students undergoing their rotation in ophthalmology were taught the actions of the extraocular muscles either without the memory aid (control group) or with it (test group). The students were surveyed one week and one month later to determine their ability to recall the muscle actions and asked to subjectively rate the usefulness of the memory aid. RESULTS: Approximately 40% of the test group used the memory tool. Eighty-seven percent of the respondents recommended that the memory aid be taught in the future. Overall, there was no significant difference in the ability to recall the actions of the muscles between the control and test groups. However, those students who found the memory aid helpful had significantly better recall than those who did not. CONCLUSION: The memory aid may be useful to a significant proportion of students.

The importance of cytokines analysis in the diagnosis of vitreoretinal lymphoma.

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.

Infectious Knockdown of CREB and HIF-1 for the Treatment of Metastatic Uveal Melanoma.

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's dependence on glycolysis for tumor progression.

The impact of monocular vision on motor function and quality of life in survivors of retinoblastoma.

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.

Subretinal Fluid Optical Density and Spectral-Domain Optical Coherence Tomography Characteristics for the Diagnosis of Circumscribed Choroidal Hemangioma.

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.

A novel combinatorial treatment option for metastatic uveal melanoma.

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.

Exploring the potential of mucin 13 (MUC13) as a biomarker for carcinomas and other diseases.

BACKGROUND: Mucin 13 (MUC13) is a cell surface glycoprotein aberrantly expressed in a variety of epithelial carcinomas. Thus far, the role of MUC13 in various diseases remains elusive. To the best of our knowledge, this is the first study to examine the potential of MUC13 as a serum biomarker in a variety of carcinomas and other conditions. METHODS: We developed a recombinant MUC13 protein, mouse monoclonal antibodies and enzyme immunoassay (ELISA) for MUC13. We used this assay to measure MUC13 levels in the supernatants of cancer cell lines and a large cohort of serum samples from healthy and diseased individuals. RESULTS: MUC13 is secreted from cancer cell lines, with highest levels found in ovarian cancer cell lines. MUC13 levels in human sera were significantly increased in patients with renal failure and 20%-30% of patients with ovarian, liver, lung and other cancers. MUC13 was also elevated in 70% of patients with active cutaneous melanoma, but not uveal melanoma. Furthermore, we identified significant MUC13 elevations in the serum of patients with vasculitis (ANCA-positive) autoantibodies, but not in those with inflammatory bowel disease. CONCLUSIONS: Serum MUC13 is frequently elevated not only in a variety of malignant cases but also in some benign pathologies, thus appearing to be a non-specific disease biomarker. Nonetheless, serum MUC13 is clearly highly elevated in some carcinoma patients, and its relationship with tumor progression in this context warrant further research. Future studies that examine the correlation between serum MUC13 levels to stage of cancer could elucidate prognostic potential.

[ADVANCES IN THE TREATMENT OF RETINOBLASTOMA AT HADASSAH IN THE LAST THREE DECADES].

INTRODUCTION: Retinoblastoma (RB) is a malignant tumor presenting in the eyes of infants and children, which endangers life, the eye and vision. The treatment of RB has undergone marked changes in recent years, and great progress has been made in our ability to preserve eyes. Over the last three decades most Israeli patients with RB have been treated in the National Specialty Ocular Oncology Service at the Hadassah-Hebrew University Medical Center in Jerusalem. AIMS: To describe advances in the primary treatment of RB with an emphasis on eye-preserving treatments. METHODS: The study included a retrospective cohort of patients who were diagnosed and treated at our center over the last three decades. Review of patients' records was approved by the Hadassah IRB. RESULTS: From 1988 to 2014 we diagnosed 290 children (138 girls - 47.6%). The mean age at diagnosis (±SE) was 18.1±1.2 months, median 12.5 months. RB was unilateral in 55.6% of the cases, bilateral in 41.3% and unilateral multifocal in 3.1%. There was an even distribution of disease severity (IRB grouping). Since the advent of IV chemotherapy (IVC) there has been a decrease in the rate of eye enucleation from ~90% to ~30% of the children until the year 2000 with a stable rate thereafter. In the years 1990-2000 there was an increase followed by a decrease in the use of primary external beam radiotherapy (EBRT), and a parallel small increase in the use of brachytherapy from the mid '90s until today. The recently introduced novel treatments - intravitreal (IVitC) and intra-arterial chemotherapy (IAC) - were used as a complimentary treatment to IVC, and not yet as a single primary modality until 2014. CONCLUSIONS: IVC replaced the need to enucleate in most of the cases, but 30% of children still require a primary enucleation. DISCUSSION: IVC usually requires additive treatments (thermal-cryotherapy, trans-pupillary thermotherapy - TTT, brachytherapy and/or local chemotherapy - IVitC and IAC) and with the use of multi-modal therapy many eyes can be preserved. In the period reported in the current manuscript, the use of IAC as a primary treatment approach was only used in isolated cases. In Summary, There have been significant advances in our ability to save eyes, and the field continues to progress.

Long-term uveal melanoma survivors: measuring their quality of life.

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.

Risk of Extraocular Extension in Eyes With Retinoblastoma Receiving Intravitreous Chemotherapy.

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.

Assessing visual function behind cataract: preoperative predictive value of the Heine Lambda 100 retinometer.

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) (ß coefficient 0.35, p<0.0001). Overall Lambda accurately (within 2 Snellen lines) estimated postoperative BCVA results in 60% of cases. The accuracy of prediction was significantly better in moderate cataracts when compared with advanced cataracts (p<0.01) with a twofold tendency towards underestimation in advanced cataracts. A Lambda ≥0.5 decimal has a calculated positive predictive value of 82% and a negative predictive value of 40% for predicting postoperative BCVA outcome ≥0.5 decimal. CONCLUSIONS: Lambda may be used to relatively accurately predict postoperative BCVA in cataract patients, specifically in those with moderate cataracts.