Vitrectomy for endophthalmitis: 5-year study of outcomes and complications

Background/Aims: To analyse the complications and outcomes of vitrectomy surgery for endophthalmitis. Methods This was a retrospective case series. All cases that underwent 23-gauge vitrectomy surgery for endophthalmitis at a tertiary centre between 1 February 2013 and 1 February 2018 were included. Main outcome measures were as follows: visual acuity (VA) at final visit and post-vitrectomy complications. / Results: 33 patients were included in the study with 20 men and 13 women, average age 63 years. Main post-surgical causes for endophthalmitis included phacoemulsification (n=9), trabeculectomy (n=5), intravitreal injection (n=5), corneal graft (n=4), vitreoretinal surgery (n=3) and endogenous endophthalmitis (n=6). Average follow-up was 18 months (SD 14). 21/33 (64%) patients had baseline perception of light VA. Analysis of exogenous endophthalmitis cases only demonstrated: mean LogMAR VA improved significantly from 2.68 to 1.66 (p=0.001). At final follow-up, 12% had VA of 6/12 or better, and 28% had VA of 6/36 or better. Vitrectomy within 7 days resulted in improved final VA outcomes (1.49 vs 2.16 LogMAR, p=0.032). Complications included retinal detachment (24.2%), macular hole (3%), hypotony (6%), suprachoroidal haemorrhage (3%) and enucleation/ evisceration (6%). / Conclusion: Vitrectomy for endophthalmitis leads to VA gains in some cases. Surgical outcomes may be improved with early vitrectomy performed within 7 days of the initial event for exogenous endophthalmitis. Patients should be advised of the potential risk of severe complications with/ and without surger

Detecting Progression of Treated Choroidal Melanomas: Is Ultrasonography Necessary?

Prompt detection and treatment of local treatment failure after radiotherapy for choroidal melanoma optimises any opportunities for conserving vision and the eye, possibly reducing an increased risk of metastatic disease. Long-term surveillance is therefore required but is hampered by the perceived need to perform ultrasonography, which may not be available at a patient’s local hospital. The aim of this study was to determine whether local treatment failure can reliably be detected with colour fundus photography alone, and, if so, in which patients. Patients were included in the study if diagnosed with local treatment failure between April 2016 and February 2021 after eye-conserving therapy for choroidal melanoma. Wide-field colour and fundal autofluorescence (FAF) images, optical coherence tomography (OCT), and ultrasonography (US) were analysed by two of the authors (GN and UH). The cohort included 87 patients with local treatment failure. In 75 patients with clear media, tumour progression was detected by colour photography alone in 74 (98.7%) patients. Sensitivity was not increased by the addition of either OCT or AF. One patient with clear media developed extraocular extension detected with US without visible change in the intraocular part of the tumour. In the other 12 patients, US was required because of opaque media and a consequently poor fundal view. Local treatment failure after radiotherapy for choroidal melanoma is detected in 98.7% of cases with colour photography when the media are clear. Ultrasonography is useful when photography is prevented by opaque media or tumours having locations in the far periphery

Survival analysis following enucleation for uveal melanoma

OBJECTIVES: To determine survival outcomes following enucleation for uveal melanoma. To compare these outcomes with the 8th edition AJCC classification and determine the influence of cytogenetics, using Fluorescent in situ Hybridisation (FISH), on survival. To determine whether failure to gain sufficient sample for cytogenetics using Fine Needle Aspiration Biopsy (FNAB) correlates with survival. SUBJECTS/METHODS: All patients undergoing primary enucleation for uveal melanoma at Moorfields Eye Hospital between 2012 and 2015 were included. Clinical, pathological, cytological and survival data were analysed for all patients. RESULTS: In total, 155 subjects were included. Mean age at enucleation was 65.9 years (SD 14.13). 88 (56.8%) patients died at a mean of three (SD 1.9) years following enucleation. Of these, 52 (33.5%) died from metastatic melanoma, 16 (10.3%) from other causes and 20 (12.9%) causes of death were unknown. Cumulative incidence analysis demonstrated AJCC grade, chromosome 8q gain and monosomy three all predict metastatic mortality. The greatest 5-year mortality rate (62%, SD10.1%) was in those with both chromosome abnormalities and AJCC stage III (Stage IV patients excluded due to low numbers). Largest basal diameter and chromosome status, both independently (p = 0.02 and p < 0.001) predicted metastatic mortality on multivariable regression analysis. Those who had an insufficient sample of cells gained during FNAB (n = 16) had no different prognosis. CONCLUSIONS: This study confirms, in this population, the poor survival of patients enucleated for uveal melanomas. It confirms the prognostic utility of adding AJCC grade to cytogenetic information. It demonstrates that the lack of sample in patients undergoing FNAB is not related to prognosis

Adjuvant External Beam Radiotherapy Following Enucleation of Eyes With Extraocular Extension From Uveal Melanoma

PURPOSE: To report local disease control and all-cause mortality in patients with extraocular extension (EOE) of uveal melanoma undergoing enucleation followed by observation or external beam radiotherapy (EBRT). METHODS: Charts of patients enucleated between January 1, 1997 and December 31, 2019, with histopathological evidence of EOE of uveal melanoma were reviewed. RESULTS: The cohort comprised 51 patients with a mean age of 67 ± 15 years, 22 (43%) of whom underwent adjuvant postenucleation EBRT. Risk factors for metastasis included presence of epithelioid cells (29/45; 88%), closed loops (20/43; 47%), monosomy 3 (16/25; 64%), and gain of 8q (20/22; 91%). Patients undergoing EBRT had more extensive EOE (median: 5.1 mm vs. 2.6 mm, p = 0.008) and surgical excision was less likely to be histologically complete (2/20; 10% vs. 14/25; 56%, p = 0.002). Local side effects following EBRT were seen in 64% (14/22). At latest follow up, 59% of patients (30/51) were alive, with a median follow up of 1.8 years (interquartile range: 2.9; range: 0.1-6.5]. By Kaplan-Meier survival analysis, the 5- and 10-year overall survival rates were 56% and 12%, respectively. There was no difference in all-cause mortality between those receiving adjuvant EBRT and those who were observed (log rank, p = 0.273). No cases of orbital recurrence were documented. CONCLUSIONS: Orbital EBRT causes significant morbidity. Cases with relatively small EOE undergoing enucleation can be safely observed, without adjuvant EBRT. Multicenter studies are required to better assess the role of EBRT when EOE is more extensive

Rate-dependent Ca2+ signalling underlying the force-frequency response in rat ventricular myocytes: A coupled electromechanical modeling study

Rate-dependent effects on the Ca2+ sub-system in a rat ventricular myocyte are investigated. Here, we employ a deterministic mathematical model describing various Ca2+ signalling pathways under voltage clamp (VC) conditions, to better understand the important role of calmodulin (CaM) in modulating the key control variables Ca2+/calmodulin-dependent protein kinase-II (CaMKII), calcineurin (CaN), and cyclic adenosine monophosphate (cAMP) as they affect various intracellular targets. In particular, we study the frequency dependence of the peak force generated by the myofilaments, the force-frequency response (FFR). Our cell model incorporates frequency-dependent CaM-mediated spatially heterogenous interaction of CaMKII and CaN with their principal targets (dihydropyridine (DHPR) and ryanodine (RyR) receptors and the SERCA pump). It also accounts for the rate-dependent effects of phospholamban (PLB) on the SERCA pump; the rate-dependent role of cAMP in up-regulation of the L-type Ca2+ channel (ICa;L); and the enhancement in SERCA pump activity via phosphorylation of PLB.Our model reproduces positive peak FFR observed in rat ventricular myocytes during voltage-clamp studies both in the presence/absence of cAMP mediated -adrenergic stimulation. This study provides quantitative insight into the rate-dependence of Ca2+-induced Ca2+-release (CICR) by investigating the frequency-dependence of the trigger current (ICa;L) and RyR-release. It also highlights the relative role of the sodium-calcium exchanger (NCX) and the SERCA pump at higher frequencies, as well as the rate-dependence of sarcoplasmic reticulum (SR) Ca2+ content. A rigorous Ca2+ balance imposed on our investigation of these Ca2+ signalling pathways clarifies their individual roles. Here, we present a coupled electromechanical study emphasizing the rate-dependence of isometric force developed and also investigate the temperature-dependence of FFR. Our model provides mechanistic biophysically based explanations for the rate-dependence of CICR, generating useful and testable hypotheses. Although rat ventricular myocytes exhibit a positive peak FFR in the presence/absence of beta-adrenergic stimulation, they show a characteristic increase in the positive slope in FFR due to the presence of Norepinephrine or Isoproterenol. Our study identifies cAMP-mediated stimulation, and rate-dependent CaMKII-mediated up-regulation of ICa;L as the key mechanisms underlying the aforementioned positive FFR

The natural history of conjunctival naevi in children and adolescents

OBJECTIVE: The objective of this study is to characterise the natural history of conjunctival naevi in a paediatric and adolescent population. METHODS: All children and adolescents referred to Moorfields Ocular Oncology Service for evaluation between January 2015 and 2020 were included. Exclusion criteria included age >20 years old and lack of anterior segment photographs. A total of 77 patients were included with a mean age of 12 years (standard deviation: 3.9; range, 4-20). The main outcome measures were: number of conjunctival naevi that grew, changed in pigmentation, required excisional biopsy, or were histologically malignant. If there was growth, the percentage increase in size was measured. RESULTS: At their first visit, 13% of patients (10/77) were discharged to local follow-up and 10% (8/77) proceeded to excisional biopsy, four further patients underwent excisional biopsy after a period of follow-up. On histopathological assessment, 92% (11/12) of lesions were benign conjunctival naevi. One patient, who had suspicious clinical features at presentation, had conjunctival melanoma. Fifty-nine patients were followed over a median of 1.1 years (interquartile range: 1.54; range, 3 months to 4 years). Eight per cent (5/59) of conjunctival naevi enlarged in diameter by a mean percentage increase in size of 2%, whereas 5% (3/59) showed increased pigmentation and 8.5% (5/59) showed decreased pigmentation. CONCLUSIONS: Growth of conjunctival naevi in children is infrequent (8%) and the large majority of those excised are benign. Because of a lack of evidence, these patients are often followed for years in ophthalmic practice. This series demonstrates that prolonged follow-up may not be necessary