A Novel Technique Using Paretic Superior Rectus as a Globe Suspender for Monocular Elevation Deficiency.

Surgical innovations in strabismus provide opportunities to improve visual function, eye alignment, and cosmesis in rare pediatric ophthalmological conditions. Monocular elevation deficiency is a rare and multifactorial disease in which the affected eye is equally limited in terms of elevation during adduction and abduction. We aimed to present a novel procedure for the treatment of acquired monocular elevation deficiency using the paretic superior rectus muscle as a globe suspender to resolve hypotropia. We report the case of an eight-year-old girl with left eyelid ptosis and hypotropia two months after draining a left orbital abscess. Left inferior rectus muscle recession was performed at five years, with residual left hypotropia. Ophthalmological examination revealed a best-corrected visual acuity of 20/20 OD and 20/100 OS. Severe left eyelid ptosis and poor levator function were also observed. Extraocular motility showed left hypotropia of 40 prism diopters with the left superior rectus muscle under action (-4) in the adduction and abduction positions. A force duction test negative for restrictions on the inferior rectus muscle was performed intraoperatively. To reduce the risks of the Knapp procedure, the left superior rectus muscle was split into medial and temporal halves. Double-armed sutures were secured in half, and the halves were detached from the sclera. The medial and temporal halves were reattached anteriorly to the medial and lateral rectus insertions, respectively. Eight weeks after surgery, the patient had nine prism diopters of hypotropia in the primary gaze. Ten weeks after surgery, there was no change in visual acuity. In the cover test, the patient exhibited residual left hypotropia of nine prism diopters with a restriction (-4) of elevation in adduction and abduction. The parents were pleased with the satisfactory cosmetic outcomes, and postoperative clinical photographs of the patient showed improved hypotropia and persistent minimal elevation of the left eye during adduction and abduction. Superior rectus muscle splitting and vertical transposition to the medial and lateral rectus could be safer and simpler alternatives to the Knapp procedure and may offer a lower risk of anterior segment ischemia. Further studies are required to confirm these findings.

State of the Art of Pharmacological Activators of p53 in Ocular Malignancies.

The pivotal role of p53 in the regulation of a vast array of cellular functions has been the subject of extensive research. The biological activity of p53 is not strictly limited to cell cycle arrest but also includes the regulation of homeostasis, DNA repair, apoptosis, and senescence. Thus, mutations in the p53 gene with loss of function represent one of the major mechanisms for cancer development. As expected, due to its key role, p53 is expressed throughout the human body including the eye. Specifically, altered p53 signaling pathways have been implicated in the development of conjunctival and corneal tumors, retinoblastoma, uveal melanoma, and intraocular melanoma. As non-selective cancer chemotherapies as well as ionizing radiation can be associated with either poor efficacy or dose-limiting toxicities in the eye, reconstitution of the p53 signaling pathway currently represents an attractive target for cancer therapy. The present review discusses the role of p53 in the pathogenesis of these ocular tumors and outlines the various pharmacological activators of p53 that are currently under investigation for the treatment of ocular malignancies.

Ocular Survival Following Intravitreal Melphalan as Adjuvant Treatment for Vitreous Retinoblastoma Seeding.

Purpose: To evaluate the efficacy of intravitreal chemotherapy for vitreous seeding in patients with retinoblastoma (Rb). Design: Retrospective, single-arm cohort study. Methods: This study was conducted at a tertiary eye center. Between 2013 and 2021, 27 patients (27 eyes) with vitreous Rb receiving adjuvant intravitreal melphalan (IVM) as secondary/salvage treatment in one eye were included. Patients who were unable to follow-up or treated elsewhere were excluded. Survival analysis was performed to assess the incidence of enucleation in the melphalan-treated group, as well as in bilateral cases with eyes receiving melphalan and those receiving standard treatment, consisting of chemotherapy, thermotherapy, and enucleation according to the disease stage. Results: The median (interquartile range) follow-up time was 65 months (range, 34-83 months). Seventeen patients (63%) had bilateral disease. Sixteen eyes (59%) were saved. The Kaplan-Meier survival estimates for eyes receiving melphalan were 100% at 1 year (95% confidence interval [CI]:11.2-14.3), 75% (95% CI:14.2-48.9) at 3 years, and 50% at 5 years. Melphalan-treated patients with bilateral disease showed a significantly higher number of saved eyes than the standard treatment group (P=0.002). Tumor recurrence was the primary cause of enucleation, accounting for 36% of the cases. In the vitreous hemorrhage group, the odds of enucleation were 13 times higher (95% CI:1.04-165.28) than in the group without this condition. Conclusion: IVM is an effective treatment option for vitreous seeds. After 3 years of follow-up, the estimated survival rate for saved eyes decreased, and vitreous hemorrhage significantly increased the likelihood of enucleation. Further studies are required to determine the precise effects of IVM.

MDM2 inhibitors-mediated disruption of mitochondrial metabolism: A novel therapeutic strategy for retinoblastoma.

MDM2 is the principal inhibitor of p53, and MDM2 inhibitors can disrupt the physical interaction between MDM2 and p53. The half-life of p53 is very short in normal cells and tissues, and an uncontrolled increase in p53 levels has potential harmful effects. It has been shown that p53 is frequently mutated in most cancers; however, p53 mutations are rare in retinoblastoma. Therefore, therapeutic strategies aimed at increasing the expression levels of wild-type p53 are attractive. In this minireview, we discuss the potential use of nutlin-3, the prototype small molecule inhibitor that disrupts the MDM2-p53 interaction, for the treatment of retinoblastoma. Although p53 has pleiotropic biological effects, the functions of p53 depend on its sub-cellular localization. In the nucleus, p53 induces the transcription of a vast array of genes, while in mitochondria, p53 regulates mitochondrial metabolism. This review also discusses the relative contribution of p53-mediated gene transcription and mitochondrial perturbation for retinoblastoma treatment.

Clinicopathological Correlations in Enucleated Globes of Late-Stage Coats Disease with a Review of the Literature.

BACKGROUND: Coats disease may cause diagnostic dilemma because of its variable clinical presentation that can be suspicious of retinoblastoma. Late sequelae of the disease are blinding with possible enucleation. We demonstrate the main histopathological findings of Coats enucleated eyes with literature review. METHODS: This was a retrospective study of all enucleated globes diagnosed as Coats disease over 30 years and were reviewed by two pathologists. The corresponding demographic data, clinical presentation, pre-operative clinical impression, and indication for enucleation were collected. Descriptive analysis of our own series data was performed. Our findings were then correlated to published data that were collected from 1983 to 2021 from the PUBMED database in English-written language. Shields classification was used as an inclusion criterion for the published reports to be analyzed. RESULTS: We had seven enucleated globes with Coats disease. Mean age at presentation was 3.2 years (range 3 months to 9 years). Male predominance was observed in 6 and all cases were unilateral. Strabismus was the most common initial presentation (57%, n = 4), followed by leukocoria (43%, n = 3). Indication for enucleation was mostly suspected retinoblastoma (57%, n = 4). Four eyes were classified as stage 4, and 2 had advanced stage 5 changes. Histopathologically, subretinal fluid with lipid-laden macrophages was seen in all cases, the anterior chamber was shallow in 5/7 with angle neovascularization in 2/7. Telangiectatic vessels were clearly observed in 4/7. CONCLUSION: Coats disease is a potentially visually disabling disease that is mostly unilateral in 95%, has male predominance of 81%, and wide age range with a mean of 17 years. In Saudi Arabia, the disease seems to present at younger age, tends to be more advanced, and may be indistinguishable from retinoblastoma at the time of diagnosis. Shields staging of Coats is highly recommended to be followed clinically to unify the pathways for treatment and to correlate the concluded outcomes.

Endophthalmitis Post Pars Plana Vitrectomy Surgery: Incidence, Organisms' Profile, and Management Outcome in a Tertiary Eye Hospital in Saudi Arabia.

PURPOSE: To determine the incidence of endophthalmitis after pars plana vitrectomy (PPV), organisms' profile, and management outcomes at a tertiary eye hospital in a Middle East country. METHODS: In this single-arm cohort study conducted in 2020, medical records of patients who underwent PPV not accompanied by any other intraocular surgery were reviewed; those with a diagnosis of acute endophthalmitis in the immediate postoperative period (within 6 weeks) during the past 6 years were analyzed. RESULTS: A total of 8153 records of PPV surgeries were reviewed. Five cases had endophthalmitis post-PPV with an incidence of 0.061%. Three (0.037%) had positive cultures, all of them for Staphylococcus epidermidis. The interval between PPV and diagnosis of endophthalmitis ranged from 3 to 25 days (mean, 15.8 days). Final vision after treatment ranged from 20/400 to no light perception, and one eye was eviscerated. CONCLUSION: The incidence of endophthalmitis post PPV is low. Despite prompt diagnosis and standard management, visual prognosis seems to be poor. The infective agents for endophthalmitis were commensals from the ocular surface.

Bilateral Retinoblastoma Presenting in an in vitro Fertilization Infant with Retinopathy of Prematurity.

Retinopathy of prematurity (ROP) and retinoblastoma (RB) are well-described entities in premature babies. Although their pathogeneses are different, with ROP representing a disorder of interrupted development and RB a genetic disease, a few co-occurring cases have been reported, raising the possibility that the 2 conditions. Here, we report the sixth such case of co-occurring ROP and RB in an 8-month-old infant conceived by in vitro fertilization (IVF) who developed bilateral retinoblastoma a few months after treatment for advanced-stage ROP. While the ROP was initially adequately managed, bilateral RB necessitated bilateral enucleation. This case raises a number of important questions about whether IVF, ROP, and RB are causally related. Although the associations between IVF, ROP, and RB are likely to be coincidental, this case nevertheless highlights that ROP patients require regular follow-up for early diagnosis and treatment of ocular sequelae including RB.

Histopathological assessment of optic nerve invasion guided by radiological findings in enucleated globes with retinoblastoma.

BACKGROUND: Optic nerve (ON) invasion is an important high-risk feature, and an indicator for neoadjuvant chemotherapy and prognosis. We aim through this study to correlate the detected-ON invasion by Magnetic resonance imaging (MRI) with the corresponding confirmed histopathological level of invasion. METHODS: A retrospective study of enucleated globes with the diagnosis of retinoblastoma received in the histopathology department(s) from January 2015 to December 2016 (2 years). Slides were reviewed for ON invasion assessment, charts were reviewed for basic demographic data. All patients underwent MRI under sedation upon diagnosis and MRI findings were collected for the above correlation. RESULTS: A total of 38 patients were included: 21 males and 17 females. 29 (77.3%) had unilateral involvement, 7 (18.4%) had bilateral involvement and 2 cases had trilateral disease. The overall mean age at diagnosis was 22.63 ± 15.15 months. Histopathological examination revealed ON invasion in 28 cases (74%) distributed as follows: prelaminar (31.6%), laminar (18.4%), and post-laminar (23.7%). MRI confirmed post-laminar ON invasion in 8 cases (true positive) but failed to detect this in 1 case. Additionally, MRI detected another 8 cases of ON invasion that were false positive on histopathology (accuracy: 63.3%; sensitivity: 88.9%; specificity: 72.4%; Positive predictive value (PPV): 50%; Negative predictive value (NPV): 95.5%). CONCLUSIONS: MRI is found to be less sensitive in evaluating prelaminar and laminar ON invasion (0.0 and 42.9%) compared to post-laminar invasion (88.9%). MRI has generally better specificity in detecting ON invasion irrespective of the invasion level. In our study, obtaining deeper and/or additional histologic sections from the other surface of the tissue block in cases where a post-laminar ON invasion by MRI is found but not confirmed histopathologically in routine sections is essential to avoid missing such an important high-risk feature.

High-risk features in primary versus secondary enucleated globes with advanced retinoblastoma: a retrospective histopathological study.

PURPOSE: The management of bilateral advanced retinoblastoma (RB) cases is challenging with attempts to use neoadjuvant therapy salvaging of one of the globes. Our aim in this study was to demonstrate the effect of this primary therapy on the histopathological features and risk factors in secondary enucleated compared to primarily enucleated globes with groups D and E RB. METHODS: We retrospectively reviewed all enucleated globes with advanced RB received in the pathology laboratories over a period of 5 years. Patients were divided into two groups: one with primary enucleations and another with at least one secondary enucleated globe, and their demographic and clinical data were analyzed. The enucleated globes in the two groups were analyzed to compare the general histopathological features including tumor seeding, size, differentiation, growth pattern, mitotic figures, and focality. More importantly, high-risk features: choroidal invasion, optic nerve (ON) invasion, iris/anterior chamber invasion, ciliary body invasion, and scleral and extra-scleral extension, as well as the pathological classification of the tumor (pT) according to the American Joint Committee on Cancer 7th edition were also compared between the two groups. RESULTS: We had a total of 106 enucleated globes (78 primary and 28 secondary enucleations) from 99 patients with advanced RB (73 patients with primarily and 26 with secondarily enucleated globes). Demographic and clinical profiles of patients were similar in both, but the mean interval from presentation to enucleation was significantly longer in the secondary enucleations (P = 0.015). Rare/occasional mitotic figures were observed in secondary enucleations using multivariate analysis (P = 0.003). Primarily enucleated globes had higher risk of tumor seeding (P = 0.020), post-laminar/surgical margin ON invasion (P = 0.001), and massive choroidal invasion (P = 0.028). Half of the secondary enucleated globes had tumors confined to the globes without invasion (pT1) and statistically significant lower tumor classifications (pT1 or pT2a) compared to primary enucleations (P =0.001). However, 18% of the secondarily enucleated globes in 3 patients had unfavorable outcome with RB-related mortality after a period of 1-4 years. CONCLUSIONS: Secondary enucleated globes with advanced RB show favorable histopathological findings mainly less mitosis. These eyes have significantly lower chance for harboring choroidal and ON invasion, thus mostly classified as pT1 or pT2a when compared to primarily enucleated globes. The decision for secondary enucleation was observed to be significantly delayed (8.0 months ± 9.8). Prompt decision for needed enucleation based on the response to primary treatment and careful histopathological examination of enucleated globes are essential to prevent disease-related mortality.

Efficacy of vincristine and carboplatin as chemo-reduction for advanced bilateral retinoblastoma, the Saudi experience.

PURPOSE: To evaluate the efficacy of a 2-drug chemotherapy regimen without external-beam radiotherapy (EBRT) and/or without enucleation in bilateral retinoblastoma. METHODS: From 1996 to 2010, 79 patients were diagnosed with bilateral RB and were eligible for chemotherapy. Chemotherapy was administered prior to and/or following local therapy to the eye. All patients received 3 cycles of chemo-reduction with carboplatin and vincristine, additional cycles of the same or other chemotherapy, local therapy, EBRT and enucleation were determined according to re-evaluation by the ophthalmologist. RESULTS: Advanced disease was seen in 115 (79%) eyes (group IV and V: 96, Group D and E: 19) out of 146 affected eyes. Tumor response after chemotherapy was observed in 78 patients (98.7%); complete response in 25 (32.1%), partial response in 49 (62.8%) Four (5.1%) had progressive disease. A total of 50 (63.3%) patients required EBRT; 38 for persistent disease, 4 for progressive disease, 2 for new lesions, 2 for re-activation and 4 for disease control. Enucleation was required in 15 (19%). Secondary malignancies occurred in two patients who underwent EBRT; one osteogenic sarcoma and one rhabdomyosarcoma then later osteogenic sarcoma. The 10 year overall survival was 96.3% with a median follow-up time of 3.124 ± 0.536 years (95%CI: 2.074-4.174). CONCLUSIONS: The 2-drug chemotherapy regimen combined with local therapy appears to be adequate therapy for low stage disease but not in patients with advanced disease. The occurrence of secondary cancers in this group of patients is worrisome further highlighting the deleterious effects of EBRT.