Expression of Cell Cycle Markers and Proliferation Factors during Human Eye Embryogenesis and Tumorigenesis.

The expression pattern of the markers p19, Ki-67, MSX1, MSX2, PDL1, pRB, and CYCLINA2 was quantitatively and semiquantitatively analyzed in histologic sections of the developing and postnatal human eye at week 8, in retinoblastoma, and in various uveal melanomas post hoc studies by double immunofluorescence. The p19 immunoreactivity characterized retinal and/or choroidal cells in healthy and tumor tissues: expression was lower in the postnatal retina than in the developing retina and retinoblastoma, whereas it was high in epithelioid melanomas. Ki67 expression was high in the developing eye, retinoblastoma, and choroidal melanomas. MSX1 and MSX2 expression was similar in the developing eye and retinoblastoma, whereas it was absent in the postnatal eye. Their different expression was evident between epithelioid and myxoid melanomas. Similarly, PDL1 was absent in epithelioid melanomas, whereas it was highly expressed in developing and tumor tissues. Expression of pRB and CYCA2 was characteristic of developing and tumorous eye samples but not of the healthy postnatal eye. The observed expression differences of the analyzed markers correlate with the origin and stage of cell differentiation of the tissue samples. The fine balance of expression could play a role in both human eye development and ocular tumorigenesis. Therefore, understanding their relationship and interplay could open new avenues for potential therapeutic interventions and a better understanding of the mechanisms underlying the developmental plasticity of the eye and the development of neoplasms.

Pars plana vitrectomy versus scleral buckling for repairing simple rhegmatogenous retinal detachments.

BACKGROUND: Rhegmatogenous retinal detachment (RRD) is a separation of neurosensory retina from the underlying retinal pigment epithelium. It is caused by retinal tears, which let fluid pass from the vitreous cavity to the subretinal space. Pars plana vitrectomy (PPV), scleral buckling surgery and pneumatic retinopexy are three accepted management strategies whose efficacy remains controversial. Pneumatic retinopexy is considered in a separate Cochrane Review. OBJECTIVES: The primary objective of this review was to assess the efficacy of PPV versus scleral buckling for the treatment of simple RRD (primary RRD of any extension with up to two clock hours large break(s) regardless of their anterior/posterior localisation) in people with (phakia) or without (aphakia) a natural lens in the eye, or with an artificial lens (pseudophakia). A secondary objective was to assess any data on economic and quality-of-life measures. SEARCH METHODS: We searched CENTRAL, which contains the Cochrane Eyes and Vision Trials Register; MEDLINE; Embase; LILACS; the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. The date of the search was 5 December 2018. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing PPV versus scleral buckling surgery with at least three months of follow-up. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. Two review authors independently extracted the data and study characteristics from the studies identified as eligible after initial screening. We considered the following outcomes: primary retinal reattachment, postoperative visual acuity, final anatomical success, recurrence of retinal detachment, number of interventions needed to achieve final anatomical success, quality of life and adverse effects. We assessed the certainty of evidence using GRADE. MAIN RESULTS: This review included 10 RCTs (1307 eyes of 1307 participants) from Europe, India, Iran, Japan and Mexico, which compared PPV and scleral buckling for RRD repair. Two of these 10 studies compared PPV combined with scleral buckling with scleral buckling alone (54 participants). All studies were high or unclear risk of bias on at least one domain. Five studies were funded by non-commercial sources, while the other five studies did not report source of funding.There was little or no difference in the proportion of participants who achieved retinal reattachment at least 3 months after the operation in the PPV group compared to those in the scleral buckling group (risk ratio (RR) 1.07, 95% confidence intervals (CI) 0.98 to 1.16; 9 RCTs, 1261 participants, low-certainty evidence). Approximately 67 in every 100 people treated with scleral buckling had retinal reattachment by 3 to 12 months. Treatment with PPV may result in 4 more people with retinal reattachment in every 100 people treated (95% confidence interval (CI) 2 fewer to 11 more).There was no evidence of any important difference in postoperative visual acuity between participants in the PPV group compared to those in the scleral buckling group (mean difference (MD) 0.00 logMAR, 95% CI -0.09 to 0.10, 6 RCTs, 1138 participants, low-certainty evidence).There was little or no difference in final anatomical success between participants in the PPV group and scleral buckling group (RR 1.01, 95% CI 0.99 to 1.04, 9 RCTs, 1235 participants, low-certainty evidence). There were 94 out of 100 people treated with control (scleral buckling) that achieved final anatomical success compared to 96 out of 100 in the PPV group.Retinal redetachment was reported in fewer participants in the PPV group compared to the scleral buckling group (RR 0.75 (95% CI 0.59 to 0.96, 9 RCTs, 1320 participants, low-certainty evidence). Approximately 28 in every 100 people treated with scleral buckling had retinal detachment by 3 to 36 months. Treatment with PPV may result in seven fewer people with retinal detachment in every 100 people treated (95% CI 1 to 11 fewer).Participants treated with PPV on average needed fewer interventions to achieve final anatomical success but the difference was small and data were skewed (MD -0.20, 95% CI -0.34 to -0.06, 2 RCTs, 682 participants, very low-certainty evidence).Very low-certainty evidence on quality of life suggested that more people in the PPV group were "satisfied with vision" compared with the scleral buckling group (RR 6.22, 95% CI 0.88 to 44.09, 1 RCT, 32 participants).All included studies reported adverse effects, however, it was not always clear whether they were reported as number of participants or number of adverse effects. Cataract development or progression was more prevalent in the PPV group (RR 1.71, 95% CI 1.45 to 2.01), choroidal detachment was more prevalent in the scleral buckling group (RR 0.19, 95% CI 0.06 to 0.65) and new/iatrogenic breaks were observed only in the PPV group (RR 8.21, 95% CI 1.91 to 35.21). Estimates of the relative frequency of other adverse effects, including postoperative proliferative vitreoretinopathy, postoperative increase in intraocular pressure, development of cystoid macular oedema, macular pucker and strabismus were imprecise. Evidence for adverse effects was low-certainty evidence. AUTHORS' CONCLUSIONS: Low- or very low-certainty evidence indicates that there may be little or no difference between PPV and scleral buckling in terms of primary success rate, visual acuity gain and final anatomical success in treating primary RRD. Low-certainty evidence suggests that there may be less retinal redetachment in the PPV group. Some adverse events appeared to be more common in the PPV group, such as cataract progression and new iatrogenic breaks, whereas others were more commonly seen in the scleral buckling group such as choroidal detachment.

Cauterisation versus fibrin glue for conjunctival autografting in primary pterygium surgery (CAGE CUP): study protocol of a randomised controlled trial.

INTRODUCTION: Pterygium is a non-cancerous growth of the conjunctival tissue over the cornea that may lead to visual impairment in advanced stages, restriction of ocular motility, chronic inflammation and cosmetic concerns. Surgical removal is the treatment of choice, but recurrence of pterygium is a frequent problem. It has been previously shown that fibrin glue may result in less recurrence and may take less time than sutures for fixing the conjunctival graft in place during pterygium surgery. However, fibrin glue is a biological material and it carries the risk of transmitting infectious agents from pooled and single-donor blood donors and anaphylaxis in susceptible individuals. Cauterisation is another surgical option, and it would be advantageous to know whether cauterisation may be superior surgical option compared with fibrin glue. This protocol describes the rationale and design of the randomised controlled trial (RCT) in which we will compare cauterisation versus fibrin glue for conjunctival autografting in primary pterygium surgery. METHODS AND ANALYSES: This will be a parallel group RCT comparing cauterisation versus fibrin glue for conjunctival autografting in primary pterygium surgery. Computer-generated randomisation will be used, and allocation concealment will be conducted using sequentially numbered opaque sealed envelopes. Surgeons will not be blinded to the procedures, but participants, other investigators and outcome assessors will be blinded. Adult participants with primary pterygium operated in a tertiary hospital in Split, Croatia, will be included. Primary outcome will be recurrence of pterygium, defined as any regrowth of tissue from the area of excision across the limbus onto the cornea after 180 days. ETHICS AND DISSEMINATION: The trial was approved by the ethics review board of the University Hospital Split (500-03/17-01/68). Results will be disseminated at conferences and through peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT03321201; Pre-results.

Neuronal differentiation in the early human retinogenesis.

AIM: Our study investigates the differentiation of retinal stem cells towards different neuronal subtypes during the critical period of human eye development. METHODS: Expression of the neuronal marker neurofilament 200 (NF200), tyrosine hydroxilase (TH) and choline acetyltransferase (ChAT) was seen by immunofluorescence in the 5th-12th - week stage of development in the human eye. Data was analysed by Mann-Whitney, Kruskal-Wallis and Dunn's post hoc tests. RESULTS: NF200, TH and ChAT cells appeared in the 5th/6th week and gradually increased during further development. The proportion of TH positive areas were distributed similarly to NF200, with a higher proportion in the outer neuroblastic layer. The proportion of a ChAT positive surface was highest in the 5th/6th - week whilst from the 7th week onwards, its proportion became higher in the optic nerve and inner neuroblastic layers than in the outer layer, where a decrease of ChAT positive areas were seen. CONCLUSIONS: Our study indicates a high differentiation potential of early retinal cells, which decreased with the advancement of development. The observed great variety of retinal phenotypic expressions results from a large scale of influences, taking place at different developmental stages.