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The Cochrane Database of Systematic... Mar 2023Diabetic retinopathy is a common complication of diabetes and a leading cause of visual impairment and blindness. Research has established the importance of blood... (Review)
Review
BACKGROUND
Diabetic retinopathy is a common complication of diabetes and a leading cause of visual impairment and blindness. Research has established the importance of blood glucose control to prevent development and progression of the ocular complications of diabetes. Concurrent blood pressure control has been advocated for this purpose, but individual studies have reported varying conclusions regarding the effects of this intervention.
OBJECTIVES
To summarize the existing evidence regarding the effect of interventions to control blood pressure levels among diabetics on incidence and progression of diabetic retinopathy, preservation of visual acuity, adverse events, quality of life, and costs.
SEARCH METHODS
We searched several electronic databases, including CENTRAL, and trial registries. We last searched the electronic databases on 3 September 2021. We also reviewed the reference lists of review articles and trial reports selected for inclusion.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) in which either type 1 or type 2 diabetic participants, with or without hypertension, were assigned randomly to more intense versus less intense blood pressure control; to blood pressure control versus usual care or no intervention on blood pressure (placebo); or to one class of antihypertensive medication versus another or placebo.
DATA COLLECTION AND ANALYSIS
Pairs of review authors independently reviewed the titles and abstracts of records identified by the electronic and manual searches and the full-text reports of any records identified as potentially relevant. The included trials were independently assessed for risk of bias with respect to outcomes reported in this review.
MAIN RESULTS
We included 29 RCTs conducted in North America, Europe, Australia, Asia, Africa, and the Middle East that had enrolled a total of 4620 type 1 and 22,565 type 2 diabetic participants (sample sizes from 16 to 4477 participants). In all 7 RCTs for normotensive type 1 diabetic participants, 8 of 12 RCTs with normotensive type 2 diabetic participants, and 5 of 10 RCTs with hypertensive type 2 diabetic participants, one group was assigned to one or more antihypertensive agents and the control group to placebo. In the remaining 4 RCTs for normotensive participants with type 2 diabetes and 5 RCTs for hypertensive type 2 diabetic participants, methods of intense blood pressure control were compared to usual care. Eight trials were sponsored entirely and 10 trials partially by pharmaceutical companies; nine studies received support from other sources; and two studies did not report funding source. Study designs, populations, interventions, lengths of follow-up (range less than one year to nine years), and blood pressure targets varied among the included trials. For primary review outcomes after five years of treatment and follow-up, one of the seven trials for type 1 diabetics reported incidence of retinopathy and one trial reported progression of retinopathy; one trial reported a combined outcome of incidence and progression (as defined by study authors). Among normotensive type 2 diabetics, four of 12 trials reported incidence of diabetic retinopathy and two trials reported progression of retinopathy; two trials reported combined incidence and progression. Among hypertensive type 2 diabetics, six of the 10 trials reported incidence of diabetic retinopathy and two trials reported progression of retinopathy; five of the 10 trials reported combined incidence and progression. The evidence supports an overall benefit of more intensive blood pressure intervention for five-year incidence of diabetic retinopathy (11 studies; 4940 participants; risk ratio (RR) 0.82, 95% confidence interval (CI) 0.73 to 0.92; I = 15%; moderate certainty evidence) and the combined outcome of incidence and progression (8 studies; 6212 participants; RR 0.78, 95% CI 0.68 to 0.89; I = 42%; low certainty evidence). The available evidence did not support a benefit regarding five-year progression of diabetic retinopathy (5 studies; 5144 participants; RR 0.94, 95% CI 0.78 to 1.12; I = 57%; moderate certainty evidence), incidence of proliferative diabetic retinopathy, clinically significant macular edema, or vitreous hemorrhage (9 studies; 8237 participants; RR 0.92, 95% CI 0.82 to 1.04; I = 31%; low certainty evidence), or loss of 3 or more lines on a visual acuity chart with a logMAR scale (2 studies; 2326 participants; RR 1.15, 95% CI 0.63 to 2.08; I = 90%; very low certainty evidence). Hypertensive type 2 diabetic participants realized more benefit from intense blood pressure control for three of the four outcomes concerning incidence and progression of diabetic retinopathy. The adverse event reported most often (13 of 29 trials) was death, yielding an estimated RR 0.87 (95% CI 0.76 to 1.00; 13 studies; 13,979 participants; I = 0%; moderate certainty evidence). Hypotension was reported in two trials, with an RR of 2.04 (95% CI 1.63 to 2.55; 2 studies; 3323 participants; I = 37%; low certainty evidence), indicating an excess of hypotensive events among participants assigned to more intervention on blood pressure.
AUTHORS' CONCLUSIONS
Hypertension is a well-known risk factor for several chronic conditions for which lowering blood pressure has proven to be beneficial. The available evidence supports a modest beneficial effect of intervention to reduce blood pressure with respect to preventing diabetic retinopathy for up to five years, particularly for hypertensive type 2 diabetics. However, there was a paucity of evidence to support such intervention to slow progression of diabetic retinopathy or to affect other outcomes considered in this review among normotensive diabetics. This weakens any conclusion regarding an overall benefit of intervening on blood pressure in diabetic patients without hypertension for the sole purpose of preventing diabetic retinopathy or avoiding the need for treatment for advanced stages of diabetic retinopathy.
Topics: Humans; Diabetic Retinopathy; Blood Pressure; Macular Edema; Diabetes Mellitus, Type 2; Hypertension; Antihypertensive Agents; Randomized Controlled Trials as Topic
PubMed: 36975019
DOI: 10.1002/14651858.CD006127.pub3 -
Journal of Glaucoma Mar 2023Normal tension glaucoma patients had softer corneas than normal controls, whereas high-tension glaucoma and ocular hypertension patients had stiffer corneas. (Meta-Analysis)
Meta-Analysis
PRCIS
Normal tension glaucoma patients had softer corneas than normal controls, whereas high-tension glaucoma and ocular hypertension patients had stiffer corneas.
PURPOSE
To comprehensively identify the corneal biomechanical differences of patients with primary open angle glaucoma (POAG) and ocular hypertension (OHT) using the Ocular Response Analyzer or the Corvis ST.
METHODS
The electronic databases PubMed, Embase, and Web of Science were comprehensively searched for studies comparing corneal biomechanical differences between POAG and OHT patients with normal controls by Ocular Response Analyzer or Corvis ST. The weighted mean differences and 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed according to the subtypes of POAG, including high-tension glaucoma (HTG) and normal tension glaucoma (NTG).
RESULTS
Thirty-one case-control studies were ultimately included, with 2462 POAG patients, 345 OHT patients, and 3281 normal controls. The corneal hysteresis (CH), corneal resistance factor (CRF), and highest concavity time (HC-t) were all lower in POAG patients than in normal controls. The CH, time at the second applanation (A2t), HC-t, highest concavity radius (HC-R), and deformation amplitude at the highest concavity (HC-DA) were lower in OHT patients, while the CRF, time at the first applanation (A1t), and stiffness parameter at the first applanation (SP-A1) were greater in OHT patients than in normal controls. The subgroup analyses showed that the CH, A2t, length at the second applanation (A2L), and HC-DA were lower in HTG, and the CH, CRF, A1t, and HC-t were lower in NTG patients than in normal controls.
CONCLUSION
The corneas of NTG patients are more deformable than normal controls, whereas the corneas of HTG and OHT patients are stiffer.
Topics: Humans; Low Tension Glaucoma; Glaucoma, Open-Angle; Intraocular Pressure; Biomechanical Phenomena; Tonometry, Ocular; Glaucoma; Ocular Hypertension; Cornea
PubMed: 36583701
DOI: 10.1097/IJG.0000000000002170 -
American Journal of Ophthalmology Sep 2014To conduct a systematic review and meta-analysis of the association between blood pressure levels and hypertension with primary open-angle glaucoma and intraocular... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To conduct a systematic review and meta-analysis of the association between blood pressure levels and hypertension with primary open-angle glaucoma and intraocular pressure endpoints.
DESIGN
Systematic review with quantitative meta-analysis.
METHODS
Studies were identified by searching the PubMed and EMBASE databases. Inverse-variance weighted random-effects models were used to summarize relative risks. Subgroup analyses and meta-regression were used to explore potential sources of heterogeneity across studies.
RESULTS
Sixty observational studies were included. The pooled relative risk for primary open-angle glaucoma comparing patients with hypertension to those without hypertension was 1.16 (95% CI = 1.05-1.28), with modest heterogeneity across studies (I(2) 34.5%). Virtually all studies reported a positive association between blood pressure and intraocular pressure (IOP). The pooled average increase in IOP associated with a 10 mm Hg increase in systolic blood pressure was 0.26 mm Hg (95% CI 0.23-0.28, I(2) 30.7%), and the average increase associated with a 5 mm Hg increase in diastolic blood pressure was 0.17 mm Hg (95% CI 0.11-0.23, I(2) 90.5%).
CONCLUSIONS
In this meta-analysis, hypertension was associated with increased intraocular pressure. The association between hypertension and primary open-angle glaucoma was stronger in cross-sectional compared with case-control and longitudinal studies. Our findings support a role of increased blood pressure in elevated intraocular pressure and possibly in the development of glaucoma.
Topics: Blood Pressure; Glaucoma, Open-Angle; Global Health; Humans; Hypertension; Incidence; Intraocular Pressure; Risk Factors
PubMed: 24879946
DOI: 10.1016/j.ajo.2014.05.029 -
BMJ Open Apr 2023To compare the efficacy and safety of tube shunt implantation with trabeculectomy in the treatment of patients with glaucoma. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To compare the efficacy and safety of tube shunt implantation with trabeculectomy in the treatment of patients with glaucoma.
METHODS
A systematic literature search was performed for studies comparing tube with trabeculectomy in patients with glaucoma (final search date: 27 February 2022). Comparisons between tube and trabeculectomy were grouped by the type of tube (Ahmed, Baerveldt, Ex-PRESS and XEN). The primary endpoints included intraocular pressure (IOP), IOP reduction (IOPR), IOPR percentage (IOPR%), complete success rate (CSR), qualified success rate (QSR) and adverse events (AEs).
RESULTS
Forty-nine studies were included in this meta-analysis and presented data for 3795 eyes (Ahmed: 670, Baerveldt: 561, Ex-PRESS: 473, XEN: 199, trabeculectomy: 1892). Ahmed and Ex-PRESS were similar to trabeculectomy in terms of IOP outcomes and success rate (Ahmed vs trabeculectomy: IOPR%: mean difference (MD)=1.34 (-5.35, 8.02), p=0.69; Ex-PRESS vs trabeculectomy: IOPR%: MD=0.12 (-3.07, 3.31), p=0.94). The IOP outcomes for Baerveldt were worse than those for trabeculectomy (IOPR%: MD=-7.51 (-10.68, -4.35), p<0.00001), but the QSR was higher. No significant difference was shown for the CSR. XEN was worse than trabeculectomy in terms of IOP outcomes (IOPR%: MD=-7.87 (-13.55, -2.18), p=0.007), while the success rate was similar. Ahmed and Ex-PRESS had a lower incidence of AEs than trabeculectomy. Baerveldt had a lower incidence of bleb leakage/wound leakage, hyphaema and hypotonic maculopathy than trabeculectomy but a higher incidence of concurrent cataracts, diplopia/strabismus and tube erosion. The incidence of AEs was similar for the XEN and trabeculectomy procedures.
CONCLUSION
Compared with trabeculectomy, both Ahmed and Ex-PRESS appear to be associated with similar ocular hypotensive effects and lower incidences of AEs. However, Baerveldt and XEN cannot achieve sufficient reductions in IOP outcomes similar to those of trabeculectomy.
PROSPERO REGISTRATION NUMBER
CRD42021257852.
Topics: Humans; Trabeculectomy; Glaucoma Drainage Implants; Treatment Outcome; Glaucoma; Intraocular Pressure
PubMed: 37080625
DOI: 10.1136/bmjopen-2022-065921 -
Graefe's Archive For Clinical and... Nov 2015Glaucoma is a leading cause of irreversible blindness worldwide. A major symptom of this pathology is the loss to the visual field in a peripheral to central pattern.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Glaucoma is a leading cause of irreversible blindness worldwide. A major symptom of this pathology is the loss to the visual field in a peripheral to central pattern. Flavonoids are polyphenol compounds sourced from plants, commonly found in green tea, red wine and cocoa, and they have neuroprotective and antioxidant characteristics proposed to be advantageous within the context of glaucoma. Currently, the literature presents conflicting evidence regarding the effect of flavonoids on patients with glaucoma and ocular hypertension; hence a systematic review and meta-analysis was conducted.
METHOD
Databases included in our literature search were EMBASE (1980-present), MEDLINE Ovid, Alternative and Complementary Medicine Database (AMED), Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Central Register of Controlled Trials (CENTRAL). Meta-analysis was performed using RevMan 5 (Review Manager) 5 software, version 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen). The primary outcomes were visual field mean deviation (MD) and intraocular pressure (IOP). Secondary outcomes were ocular blood flow and blood pressure (BP).
CONCLUSION
Meta-analyses showed that flavonoids have a promising role in improving visual function in patients with glaucoma and ocular hypertension (OHT), and appear to play a part in both improving and slowing the progression of visual field loss.
Topics: Blood Pressure; Flavonoids; Glaucoma; Humans; Intraocular Pressure; Ocular Hypertension; Visual Acuity; Visual Fields
PubMed: 26340868
DOI: 10.1007/s00417-015-3168-y -
The Cochrane Database of Systematic... Feb 2017Glaucoma is a leading cause of irreversible blindness worldwide and the second most common cause of blindness after cataracts. The primary treatment for glaucoma aims to... (Review)
Review
BACKGROUND
Glaucoma is a leading cause of irreversible blindness worldwide and the second most common cause of blindness after cataracts. The primary treatment for glaucoma aims to lower intraocular pressure (IOP) with the use of topical medicines. Topical medication instillation techniques, such as eyelid closure and nasolacrimal occlusion when instilling drops, have been proposed as potential methods to increase ocular absorption and decrease systemic absorption of the drops.
OBJECTIVES
To investigate the effectiveness of topical medication instillation techniques compared with usual care or another method of instillation of topical medication in the management of glaucoma or ocular hypertension.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 12), MEDLINE Ovid (1946 to 8 December 2016), Embase Ovid (1947 to 8 December 2016), PubMed (1948 to 8 December 2016), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 8 December 2016), International Pharmaceutical Abstracts Database (1970 to 8 December 2016), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched 13 May 2013), ClinicalTrials.gov (www.clinicaltrials.gov) (searched 8 December 2016) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) (searched 8 December 2016). We did not use any date or language restrictions in the electronic searches for trials.
SELECTION CRITERIA
We included randomized controlled trials which had compared any topical medication instillation technique with usual care or a different method of instillation of topical medication.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened records from the searches for eligibility, assessed the risk of bias, and extracted data. We followed methods recommended by Cochrane.
MAIN RESULTS
We identified two trials (122 eyes of 61 participants) that had evaluated a topical medication instillation technique. We also identified two ongoing trials. Both included trials used a within-person design and administered prostaglandin monotherapy for glaucoma or ocular hypertension. Because the trials evaluated different instillation techniques and assessed different outcomes, we performed no meta-analysis.One trial, conducted in the US, evaluated the effect of eyelid closure (one and three minutes) versus no eyelid closure on lowering IOP. At one to two weeks' follow-up, reduction in IOP was similar in the eyelid closure group and the no eyelid closure group (mean difference (MD) -0.33 mmHg, 95% confidence interval (CI) -0.8 to 1.5; 51 participants; moderate-certainty evidence).The second trial, conducted in Italy, evaluated the effect of using an absorbent cloth to wipe excess fluid after instillation (fluid removal) versus not using an absorbent cloth (no removal) on reducing dermatologic adverse events. At four months' follow-up, eyelashes were shorter among eyes in the fluid removal group compared with the no fluid removal group (MD -1.70 mm, 95% CI -3.46 to 0.06; 10 participants; low-certainty evidence). Fewer eyes showed skin hyperpigmentation in the eyelid region towards the nose in the fluid removal group compared with the no removal group (RR 0.07, 95% CI 0.01 to 0.84; 10 participants; low-certainty evidence); however, the difference was uncertain in the eyelid region towards the temples (RR 0.44, 95% CI 0.07 to 2.66; 10 participants; low-certainty evidence). The effect hypertrichosis (excessive hair growth) was uncertain between groups (RR 1.00, 95% CI 0.17 to 5.98; 10 participants; low-certainty evidence).Neither trial reported other outcomes specified for this review, including the proportion of participants with IOP less than 21 mmHg; participant-reported outcomes related to the ease, convenience, and comfort of instillation techniques; physiologic measurements of systemic absorption; escalation of therapy; mean change in visual fields; optic nerve progression; mean change in best-corrected visual acuity; proportion in whom glaucoma developed; quality of life outcomes; or cost-effectiveness outcomes. Neither trial reported data at follow-up times of more than four months.
AUTHORS' CONCLUSIONS
Evidence to evaluate the effectiveness of topical medication instillation techniques for treatment of glaucoma is lacking. It is unclear what, if any, effects instillation techniques have on topical medical therapy for glaucoma.
Topics: Administration, Ophthalmic; Antihypertensive Agents; Bimatoprost; Eyelashes; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Ophthalmic Solutions; Prostaglandins F, Synthetic; Randomized Controlled Trials as Topic; Travoprost
PubMed: 28218404
DOI: 10.1002/14651858.CD010520.pub2 -
The Cochrane Database of Systematic... Jan 2015Primary congenital glaucoma (PCG) manifests within the first few years of a child's life and is not associated with any other systemic or ocular abnormalities. PCG... (Review)
Review
BACKGROUND
Primary congenital glaucoma (PCG) manifests within the first few years of a child's life and is not associated with any other systemic or ocular abnormalities. PCG results in considerable morbidity even in developed countries. Several surgical techniques for treating this condition, and lowering the intraocular pressure (IOP) associated with it, have been described.
OBJECTIVES
To compare the effectiveness and safety of different surgical techniques for PCG.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2014, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2014), EMBASE (January 1980 to June 2014), (January 1982 to June 2014), PubMed (January 1946 to June 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), the 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 June 2014.
SELECTION CRITERIA
We included all randomized and quasi-randomized trials in which different types of surgical interventions were compared in children under five years of age with PCG.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures specified by The Cochrane Collaboration.
MAIN RESULTS
We included a total of six trials (four randomized and two quasi-randomized) with 102 eyes in 61 children. Two trials were conducted in the USA and one trial each in Egypt, Israel, Lebanon and Saudi Arabia. All trials included children aged younger than one year when diagnosed with PCG, and followed them for periods ranging from six months to five years.No two trials compared the same pair of surgical interventions, so we did not perform any meta-analysis. One trial compared trabeculotomy versus goniotomy; a second trial compared combined trabeculectomy-trabeculotomy with mitomycin C versus trabeculectomy-trabeculotomy with mitomycin C and deep sclerectomy; a third trial compared combined trabeculotomy-trabeculectomy versus trabeculotomy; a fourth trial compared one goniotomy versus two goniotomies; a fifth trial compared trabeculotomy versus viscocanalostomy; and the sixth trial compared surgical goniotomy versus neodymium-YAG laser goniotomy. For IOP change and surgical success (defined by IOP achieved), none of the trials reported a difference between pairs of surgical techniques. However, due to the limited sample sizes for all trials (average of 10 children per trial), the evidence as to whether a particular surgical technique is effective and which surgical technique is better still remains uncertain. Adverse events, such as choroidal detachment, shallow anterior chamber and hyphema, were reported from four trials. None of the trials reported quality of life or economic data.These trials were neither designed nor reported well overall. Two trials were quasi-randomized trials and judged to have high risk of selection bias; four trials were at unclear or high risk for performance bias and detection bias; and we judged one trial to have high risk of attrition bias due to high proportions of losses to follow-up. Due to poor study design and reporting, the reliability and applicability of evidence remain unclear.
AUTHORS' CONCLUSIONS
No conclusions could be drawn from the trials included in this review due to paucity of data. More research is needed to determine which of the many surgeries performed for PCG are effective.
Topics: Child, Preschool; Glaucoma; Glaucoma Drainage Implants; Humans; Infant; Infant, Newborn; Mitomycin; Postoperative Complications; Randomized Controlled Trials as Topic; Sclera; Trabecular Meshwork; Trabeculectomy
PubMed: 25636153
DOI: 10.1002/14651858.CD008213.pub2 -
Acta Ophthalmologica May 2018To assess the efficacy and safety of different regimens, including monotherapy and double therapy, for primary open-angle glaucoma (POAG) or ocular hypertension. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To assess the efficacy and safety of different regimens, including monotherapy and double therapy, for primary open-angle glaucoma (POAG) or ocular hypertension.
METHODS
We searched PubMed, EMBASE and clinicaltrials.gov for studies that fit our inclusion criteria in this network meta-analysis. Randomized controlled trials that report data on efficacy and safety of medications for POAG or ocular hypertension are included. Data on intra-ocular pressure (IOP) lowering effect and incidence of adverse events including hyperaemia and ocular discomfort were extracted and used in mixed-comparison analysis.
RESULTS
This study includes 72 randomized trials. Data were available on 12 medical treatments of POAG or ocular hypertension. Of 66 possible comparisons of outcome efficacy, 15 treatments were compared directly. Compared to prostaglandin analogues (PGA), beta-blockers (BB) showed relatively weaker ability to lower IOP, followed by α2-adrenergic agonists (AA) and carbonic anhydrase inhibitors (CAI). For dual therapy, regimens composed of a combination of PGA with another treatment demonstrated more powerful IOP lowering efficacy, while the combination of two non-PGA drugs had lower efficacy in controlling IOP than PGA alone. There was no statistical significance in combinations that did not include PGA on efficacy of IOP control. In terms of tolerance, PGA alone leads to more severe hyperaemia than any other monotherapy regimen, while BBs have the lowest effect on the incidence of hyperaemia. Most dual therapy regimens containing PGA also lead to serious hyperaemia, with the exception of PGA + AA. Compared to regimens containing PGA, those with BB are less likely to cause hyperaemia.
CONCLUSION
Our network meta-analysis showed that PGAs provide best IOP lowering effect among all the monotherapy regimen. Combination of PGA and other category of drugs leads to better IOP decrease. Combination of BB and another non-PGA drug may have less ocular side-effects than PGA alone.
Topics: Antihypertensive Agents; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Network Meta-Analysis; Ocular Hypertension
PubMed: 29144028
DOI: 10.1111/aos.13568 -
EClinicalMedicine Jul 2022Glaucoma and chronic kidney disease (CKD) are prevalent and debilitating conditions, with common pathogenic pathways like oxidative stress and fluid dysregulation. We...
BACKGROUND
Glaucoma and chronic kidney disease (CKD) are prevalent and debilitating conditions, with common pathogenic pathways like oxidative stress and fluid dysregulation. We evaluated if there is a bidirectional association between them, as previous studies have yielded conflicting results.
METHODS
In this systematic review and meta-analysis, we searched PubMed, Embase and Cochrane Library from inception until 15 June 2021, including full-length English articles published in peer-reviewed journals reporting on glaucoma and CKD as either exposure or outcome, among participants aged ≥18 years. We pooled overall summary estimates of odds ratios using random-effect meta-analysis and conducted subgroup meta-analyses and univariate meta regression. We assessed risk of bias using the Newcastle-Ottawa Scale (NOS) and quality of evidence using the GRADE framework. Our article is PROSPERO-registered and adherent to both PRISMA and MOOSE guidelines. This review is registered with PROSPERO (CRD42021262846).
FINDINGS
We identified 14 articles comprising of 3 retrospective cohort studies and 12 cross-sectional studies from 2,428 records, including 1,978,254 participants. Risk of bias was low to moderate. Participants with CKD at baseline had higher pooled odds of glaucoma (odds ratio[OR]=1.18, 95% confidence interval[CI]=1.04-1.33, I=66%, N=12) compared to participants without CKD. The association remained significant in subgroups of longitudinal studies, participants with diabetes, East Asian studies and primary open-angle glaucoma. In the reverse direction, participants with glaucoma at baseline had over three-fold higher odds of incident CKD compared to participants without glaucoma after 10-15 years of follow-up in longitudinal studies (OR=3.67, 95% CI=2.16-6.24, I=75%, N=2). All studies adjusted for age and sex, while most studies adjusted for comorbidities such as diabetes and hypertension. Meta-regression identified ethnicity (East Asians vs Non-East Asians) as a significant effect moderator. Associations were robust to trim-and-fill adjustment for publication bias, single-study influence and cumulative meta-analyses.
INTERPRETATION
Our meta-analysis suggests a bidirectional relationship between glaucoma and CKD, particularly among East Asians. Further studies are required to elucidate underlying mechanisms and account for differential association by ethnicity.
FUNDING
Ching-Yu Cheng is supported by Clinician Scientist Award (NMRC/CSA-SI/0012/2017) of the Singapore Ministry of Health's National Medical Research Council.
PubMed: 35747173
DOI: 10.1016/j.eclinm.2022.101498 -
The Cochrane Database of Systematic... Jan 2023Uveitis is a term used to describe a group of intraocular inflammatory diseases. Uveitis is the fifth most common cause of vision loss in high-income countries, with the... (Review)
Review
BACKGROUND
Uveitis is a term used to describe a group of intraocular inflammatory diseases. Uveitis is the fifth most common cause of vision loss in high-income countries, with the highest incidence of disease in the working-age population. Corticosteroids are the mainstay of treatment for all subtypes of non-infectious uveitis. They can be administered orally, topically with drops, by periocular (around the eye) or intravitreal (inside the eye) injection, or by surgical implantation.
OBJECTIVES
To determine the efficacy and safety of steroid implants in people with chronic non-infectious posterior uveitis, intermediate uveitis, and panuveitis.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE Ovid, Embase, PubMed, LILACS, and three trials registries to November 2021. SELECTION CRITERIA: We included randomized controlled trials comparing either fluocinolone acetonide (FA) or dexamethasone (DEX) intravitreal implants with standard-of-care therapy or sham procedures, with at least six months of follow-up after treatment. We included studies that enrolled participants of all ages, who had chronic non-infectious posterior uveitis, intermediate uveitis, or panuveitis with vision that was better than hand-motion.
DATA COLLECTION AND ANALYSIS
We applied standard Cochrane methodology.
MAIN RESULTS
We included data from four trials (683 participants, 907 eyes) that compared corticosteroid implants with either sham or standard-of-care therapy. Study characteristics and risk of bias Of the two trials that compared corticosteroid implants with sham procedure, one examined a 0.18 mg FA implant, and the other, a 0.7 mg DEX implant. The other two trials compared a 0.59 mg FA implant with standard-of-care therapy, which included systemic corticosteroids and immunosuppressive medications, if needed. We assessed the four trials to be at either low risk, or with some concerns of risk of bias across all domains. Findings Using sham procedure as control, combined results at the six-month primary time point suggested that corticosteroid implants may decrease the risk of uveitis recurrence by 60% (relative risk [RR] 0.40, 95% confidence interval [CI] 0.30 to 0.54; 2 trials, 282 participants; low-certainty evidence); and lead to a greater improvement in best-corrected visual acuity (BCVA; mean difference [MD] 0.22 logMAR, 95% CI 0.13 to 0.31; 1 trial, 153 participants; low-certainty evidence). Evidence based on a single-study report (146 participants) suggested that steroid implants may have no effects on visual functioning quality of life, measured on the National Eye Institute 25-Item Visual Function Questionnaire (MD 2.85, 95%CI -3.64 to 9.34; 1 trial, 146 participants; moderate-certainty evidence). Using standard-of care therapy as control, combined estimates at the 24-month primary time point suggested that corticosteroid implants were likely to decrease the risk of recurrence of uveitis by 54% (RR 0.46, 95% CI 0.35 to 0.60; 2 trials, 619 eyes). Combined estimates at 24 months also suggested that steroid implants may have little to no effects on BCVA (MD 0.05 logMAR, 95% CI -0.02 to 0.12; 2 trials, 619 eyes; low-certainty evidence). Evidence based on a single-study report (232 participants) suggested that steroid implants may have minimal clinical effects on visual functioning (MD 4.64, 95% CI 0.13 to 9.15; 1 trial, 232 participants; moderate-certainty evidence); physical functioning (SF-36 physical subscale MD 2.95, 95% CI 0.55 to 5.35; 1 trial, 232 participants; moderate-certainty evidence); or mental health (SF-36 mental subscale MD 3.65, 95% CI 0.52 to 6.78; 1 trial, 232 participants; moderate-certainty evidence); but not on EuroQoL (MD 6.17, 95% CI 1.87 to 10.47; 1 trial, 232 participants; moderate-certainty evidence); or EuroQoL-5D scale (MD 0.02, 95% CI -0.04 to 0.08; 1 trial, 232 participants; moderate-certainty evidence). Adverse effects Compared with sham procedures, corticosteroid implants may slightly increase the risk of cataract formation (RR 2.69, 95% CI 1.17 to 6.18; 1 trial, 90 eyes; low-certainty evidence), but not the risk of cataract progression (RR 2.00, 95% CI 0.65 to 6.12; 1 trial, 117 eyes; low-certainty evidence); or the need for surgery (RR 2.98, 95% CI 0.82 to 10.81; 1 trial, 180 eyes; low-certainty evidence), during up to 12 months of follow-up. These implants may increase the risk of elevated intraocular pressure ([IOP] RR 2.81, 95% CI 1.42 to 5.56; 2 trials, 282 participants; moderate-certainty evidence); and the need for IOP-lowering eyedrops (RR 1.85, 95% CI 1.05 to 3.25; 2 trials, 282 participants; moderate-certainty evidence); but not the need for IOP-lowering surgery (RR 0.72, 95% CI 0.13 to 4.17; 2 trials, 282 participants; moderate-certainty evidence). Evidence comparing the 0.59 mg FA implant with standard-of-care suggested that the implant may increase the risk of cataract progression (RR 2.71, 95% CI 2.06 to 3.56; 2 trials, 210 eyes; low-certainty evidence); and the need for surgery (RR 2.98, 95% CI 2.33 to 3.79; 2 trials, 371 eyes; low-certainty evidence); along with the risk of elevated IOP (RR 3.64, 95% CI 2.71 to 4.87; 2 trials, 605 eyes; moderate-certainty evidence); and the need for medical (RR 3.04, 95% CI 2.36 to 3.91; 2 trials, 544 eyes; moderate-certainty evidence); or surgical interventions (RR 5.43, 95% CI 3.12 to 9.45; 2 trials, 599 eyes; moderate-certainty evidence). In either comparison, these implants did not increase the risk for endophthalmitis, retinal tear, or retinal detachment (moderate-certainty evidence). AUTHORS' CONCLUSIONS: Our confidence is limited that local corticosteroid implants are superior to sham therapy or standard-of-care therapy in reducing the risk of uveitis recurrence. We demonstrated different effectiveness on BCVA relative to comparators in people with non-infectious uveitis. Nevertheless, the evidence suggests that these implants may increase the risk of cataract progression and IOP elevation, which will require interventions over time. To better understand the efficacy and safety profiles of corticosteroid implants, we need future trials that examine implants of different doses, used for different durations. The trials should measure core standard outcomes that are universally defined, and measured at comparable follow-up time points.
Topics: Humans; Adrenal Cortex Hormones; Cataract; Glaucoma; Panuveitis; Quality of Life; Steroids; Uveitis; Uveitis, Intermediate; Randomized Controlled Trials as Topic
PubMed: 36645716
DOI: 10.1002/14651858.CD010469.pub3