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The Indian Journal of Medical Research Jul 2021In the current scenario, with availability of different surgical procedures for limbal stem cell deficiency (LSCD), there exists no common consensus as to the... (Review)
Review
BACKGROUND & OBJECTIVES
In the current scenario, with availability of different surgical procedures for limbal stem cell deficiency (LSCD), there exists no common consensus as to the standardization of the management protocol for the same. In addition, there also exists diversity in the views about the clinical diagnosis, ancillary investigations and clinical parameters. The objective of the present study was to evaluate the reported outcomes of surgical interventions for the management of LSCD.
METHODS
A systematic review of published literature on limbal stem cell transplantation (LSCT) was performed using Ovid Medline, Embase and PubMed for a duration of 2009 to 2019. Original studies including prospective, retrospective case series and randomized controlled trials, articles in English language, articles with access to full text and studies with more than or at least 10 patients were included in this review. Data related to clinical and visual outcomes were evaluated, and pool estimates of different surgeries were calculated using random-effects model and individually using Pearson's Chi-square test.
RESULTS
A total of 1133 abstracts were evaluated. Finally, 17 studies were included for the analysis. Among these 17 studies, direct limbal lenticule transplantation was performed in five studies, of which autologous tissue from the fellow eye [conjunctival limbal autograft (CLAU)], allograft from a cadaver/live donor [keratolimbal allograft (KLAL)/conjunctival limbal allograft (CLAL)] and combination of CLAU plus KLAL were done in one, three and one studies, respectively. The ex vivo expanded cultivated limbal epithelial transplantation (CLET) was reported in six studies and simple limbal epithelial transplantation (SLET) in four studies. Two were comparative studies comparing CLET and CLAL (living-related CLAL) with cadaveric KLAL, respectively. Outcome analysis of the included studies showed significant heterogeneity. Calculated pool rate for various types of surgeries was calculated. The pool estimate for CLAL was 67.56 per cent [95% confidence interval (CI), 41.75-93.36; I=83.5%, P=0.002]. For KLAL, this value was 63.65 per cent (95% CI, 31.38-95.91; I=92.4%, P=0.000). Pool estimate for CLET was 78.90 per cent (95% CI, 70.51-87.28; I=73.6%, P=0.001). Corresponding values for SLET were 79.08 per cent (95% CI, 74.10-84.07; I=0.0%, P=0.619). CLAU and combination of CLAU plus KLAL were done in one study each; hence, statistical analysis could not be done. The functional outcome in terms of gain in visual acuity post-operatively was better in KLAL (P<0.005) and SLET group as compared to CLET group.
INTERPRETATION & CONCLUSIONS
The present analysis suggests that though the anatomical success rates were almost identical between SLET, CLET, CLAL, and KLAL procedures, the functional success rates were better following KLAL and SLET procedures as compared to CLET. Decision for LSCT for cases of ocular burns based on either clinical judgement of the surgeon or individual diagnosis remains a suitable option.
Topics: Corneal Diseases; Humans; Limbus Corneae; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies; Stem Cell Transplantation; Stem Cells; Transplantation, Autologous
PubMed: 34782530
DOI: 10.4103/ijmr.IJMR_1139_18 -
The Cochrane Database of Systematic... Nov 2015Glaucoma is one of the leading largely preventable causes of blindness in the world. It usually is addressed first medically with topical intraocular pressure-lowering... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Glaucoma is one of the leading largely preventable causes of blindness in the world. It usually is addressed first medically with topical intraocular pressure-lowering drops or by laser trabeculoplasty. In cases where such treatment fails, glaucoma-filtering surgery is considered, most commonly trabeculectomy surgery with variations in technique, for example, the type of conjunctival flap (fornix- or limbal-based). In a fornix-based flap, the surgical wound is performed at the corneal limbus; while in a limbal-based flap, the incision is further away. Many studies in the literature compare fornix- and limbal-based trabeculectomy with respect to outcomes and complications.
OBJECTIVES
To assess the comparative effectiveness of fornix- versus limbal-based conjunctival flaps in trabeculectomy for adult glaucoma, with a specific focus on intraocular pressure (IOP) control and complications (adverse effects).
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to October 2015), EMBASE (January 1980 to October 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to October 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 23 October 2015.We reviewed the bibliographic references of identified randomised controlled trials (RCTs) in order to find trials not identified by the electronic searches. We contacted researchers and practitioners active in the field of glaucoma to identify other published and unpublished trials.
SELECTION CRITERIA
We included RCTs comparing the benefits and complications of fornix- versus limbal-based trabeculectomy for glaucoma, irrespective of glaucoma type, publication status, and language. We excluded studies on children less than 18 years of age, since wound healing is different in this age group and the rate of bleb scarring postoperatively is high.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed trial quality. We contacted study authors for additional information.The primary outcome was the proportion of failed trabeculectomies at 24 months. Failure was defined as the need for repeat surgery or uncontrolled IOP (more than 22 mmHg), despite additional topical/systemic medications. Needling and 5-fluorouracil (5-FU) injections were allowed only during the first six months postoperatively; additional needling or 5-FU injections were considered as failure. Mean post-operative IOP at 12 and 24 months also was recorded.
MAIN RESULTS
The review included six trials with a total of 361 participants. Two studies were conducted in America and one each in Germany, Greece, India, and Saudi Arabia. The participants of four trials had open-angle glaucoma; one study included participants with primary open-angle or primary closed-angle glaucoma, and one study did not specify the type of glaucoma. Three studies used a combined procedure (phacotrabeculectomy). Trabeculectomy with mitomycin C (MMC) was performed in four studies, and trabeculectomy with 5-fluorouracil (5-FU) was performed in only one study.None of the included trials reported trabeculectomy failure at 24 months. Only one trial reported the failure rate of trabeculectomy as a late complication. Failure was higher among participants randomised to the limbal-based surgery: 1/50 eyes failed trabeculectomy in the fornix group compared with 3/50 in the limbal group (risk ratio (RR) 0.33, 95% confidence interval (95% CI) 0.04 to 3.10); therefore we are very uncertain as to the relative effect of the two procedures on failure rate.Four studies including 252 participants provided measures of mean IOP at 12 months. In the fornix-based surgeries, mean IOP ranged from 12.5 to 15.5 mmHg and similar results were noted in limbal-based surgeries with mean IOP ranging from 11.7 to 15.1 mmHg without significant difference. Mean difference was 0.44 mmHg (95% CI -0.45 to 1.33) and 0.86 mmHg, (95% CI -0.52 to 2.24) at 12 and 24 months of follow-up, respectively. Neither of these pooled analyses showed a statistically significant difference in IOP between groups (moderate quality of evidence).One trial reported number of anti-glaucoma medications at 24 months of follow-up with no difference noted between surgical groups. However, three trials reported the mean number of anti-glaucoma medications at 12 months of follow-up without significant difference in the mean number of postoperative IOP-lowering medications between the two surgical techniques. Mean difference was 0.02, (95% CI -0.15 to 0.19) at 12 months of follow-up (high quality of evidence).Because of the small numbers of events and total participants, the risk of many reported adverse events were uncertain and those that were found to be statistically significant may have been due to chance.For risk of bias assessment: although all six trials were randomised selection bias was mostly unclear, with unclear random sequence generation in four of the six studies and unclear allocation concealment in five of the six studies. Attrition bias was encountered in only one trial which also suffered from reporting bias. All other trials had an unclear risk of reporting bias as there was no access to study protocols. All included trials were judged to have high risk of detection bias due to lack of masking of the outcomes. Trabeculectomy is quite a standard procedure and unlikely to induce bias due to surgeon 'performance', hence performance bias was not evaluated.
AUTHORS' CONCLUSIONS
The main result of this review was that there was uncertainty as to the difference between fornix- and limbal-based trabeculectomy surgeries due to the small number of events and confidence intervals that cross the null. This also applied to postoperative complications, but without any impact on long-term failure rate between the two surgical techniques.
Topics: Antihypertensive Agents; Fluorouracil; Glaucoma; Humans; Intraocular Pressure; Limbus Corneae; Mitomycin; Randomized Controlled Trials as Topic; Sclera; Surgical Flaps; Trabeculectomy; Treatment Failure
PubMed: 26599668
DOI: 10.1002/14651858.CD009380.pub2 -
American Journal of Ophthalmology Feb 2017To compare effectiveness of fornix- and limbal-based conjunctival flaps in trabeculectomy surgery. (Review)
Review
PURPOSE
To compare effectiveness of fornix- and limbal-based conjunctival flaps in trabeculectomy surgery.
DESIGN
Systematic review.
METHODS
Setting: CENTRAL, MEDLINE, LILACS, ISRCTN registry, ClinicalTrials.gov, WHO, and ICTRP were searched to identify eligible randomized controlled trials (RCTs).
STUDY POPULATION
RCTs in which benefits and complications of fornix- vs limbal-based trabeculectomy for glaucoma were compared in adult glaucoma patients.
OBSERVATION PROCEDURE
We followed Cochrane methodology for data extraction.
MAIN OUTCOME MEASURES
Proportion of failed trabeculectomies at 24 months, defined as the need for repeat surgery or uncontrolled intraocular pressure (IOP) >22 mm Hg, despite topical/systemic medications.
RESULTS
The review included 6 trials with a total of 361 participants, showing no difference in effectiveness between fornix-based vs limbal-based trabeculectomy surgery, although with a high level of uncertainty owing to low event rates. In the fornix-based and limbal-based surgery, mean IOP at 12 months was similar, with ranges of 12.5-15.5 mm Hg and 11.7-15.1 mm Hg, respectively. Mean difference was 0.44 mm Hg (95% CI -0.45 to 1.33) and 0.86 mm Hg (95% CI -0.52 to 2.24) at 12 and 24 months of follow-up, respectively. Mean number of postoperative glaucoma medications was similar between the 2 groups. Mean difference was 0.02 (95% CI -0.15 to 0.19) at 12 months. As far as postoperative complications, an increased risk of shallow anterior chamber was observed in the limbal-based group.
CONCLUSION
Similar efficacy of trabeculectomy surgery with respect to bleb failure or IOP control was observed in both types of conjunctival flap incisions. A significant difference was detected in the risk of postoperative shallow anterior chamber, which was increased in the limbal-based group.
Topics: Conjunctiva; Glaucoma; Humans; Limbus Corneae; Surgical Flaps; Trabeculectomy
PubMed: 27794426
DOI: 10.1016/j.ajo.2016.10.006 -
The Ocular Surface Jan 2022Animal models are pivotal for elucidating pathophysiological mechanisms and evaluating novel therapies. This systematic review identified studies that developed or...
PURPOSE
Animal models are pivotal for elucidating pathophysiological mechanisms and evaluating novel therapies. This systematic review identified studies that developed or adapted animal models of limbal stem cell deficiency (LSCD), assessed their reporting quality, summarized their key characteristics, and established their clinical translational relevance to human disease.
METHODS
The protocol was prospectively registered (PROSPERO CRD42020203937). Searches were conducted in PubMed, Ovid EMBASE and Web of Science in August 2020. Two authors screened citations, extracted data, assessed the reporting quality of eligible studies using the ARRIVE guidelines, and judged the clinical translational relevance of each model using a custom matrix.
RESULTS
105 studies were included. Rabbits were the most common animal species. Overall, 97% of studies recapitulated LSCD to a clinical etiology, however 62% did not provide sufficient methodological detail to enable independent reproduction of the model. Adverse events and/or exclusion of animals were infrequently (20%) reported. Approximately one-quarter of studies did not produce the intended severity of LSCD; 34% provided insufficient information to assess the fidelity of disease induction. Adjunctive diagnostic confirmation of LSCD induction was performed in 13% of studies.
CONCLUSIONS
This is the first systematic review to assess the reporting quality and clinical translational relevance of animal models of LSCD. Models of LSCD have evolved over time, resulting in variable reporting of the characteristics of animals, experimental procedures and adverse events. In most studies, validation of LSCD was made using clinical tests; newer adjunctive techniques would enhance diagnostic validation. As most studies sought to evaluate novel therapies for LSCD, animal models should ideally recapitulate all features of the condition that develop in patients.
Topics: Animals; Corneal Diseases; Epithelium, Corneal; Humans; Limbus Corneae; Models, Animal; Rabbits; Scleral Diseases; Stem Cells
PubMed: 34583088
DOI: 10.1016/j.jtos.2021.09.006 -
Survey of Ophthalmology 2020An accurate diagnosis of limbal stem cell deficiency (LSCD) is the premise of an appropriate treatment; however, there is no consensus about the diagnostic criteria for... (Meta-Analysis)
Meta-Analysis
An accurate diagnosis of limbal stem cell deficiency (LSCD) is the premise of an appropriate treatment; however, there is no consensus about the diagnostic criteria for LSCD. We performed a systematic literature search of the peer-reviewed articles on PubMed, Medline, and Ovid to investigate how LSCD was diagnosed before surgical intervention. The methods used to diagnose LSCD included clinical presentation, impression cytology, and in vivo confocal microscopy. Among 131 eligible studies (4054 eyes), 26 studies (459 eyes, 11.3%) did not mention the diagnostic criteria. In the remaining 105 studies, the diagnosis of LSCD was made on the basis of clinical examination alone in 2398 eyes (62.9%), and additional diagnostic tests were used in 1047 (25.8%) eyes. Impression cytology was used in 981 eyes (24.2%), in vivo confocal microscopy was used in 29 eyes (0.7%), and both impression cytology and in vivo confocal microscopy were used in 37 eyes (0.9%). Our findings suggest that only a small portion of patients underwent a diagnostic test to confirm the diagnosis of LSCD. Treating physicians should be aware of the limitations of clinical examination in diagnosing LSCD and perform a diagnostic test whenever possible before surgical intervention.
Topics: Corneal Diseases; Humans; Limbus Corneae; Microscopy, Confocal; Ophthalmologic Surgical Procedures; Stem Cells
PubMed: 31276736
DOI: 10.1016/j.survophthal.2019.06.008