Keratoconus tomographic indices in osteogenesis imperfecta.

PURPOSE: Osteogenesis imperfecta (OI) is a rare inherited disease affecting collagen-rich tissues. Ocular complications have been reported such as thin corneas, low ocular rigidity, keratoconus, among others. The purpose of this study is to characterize corneal tomographic features in OI patients compared to unaffected patients, with particular focus on commonly studied keratoconus indices. METHODS: Cross-sectional case-control study including 37 OI patients and 37 age-matched controls. Patients and controls underwent comprehensive ophthalmological examination including corneal Scheimpflug tomography with a Pentacam HR device (Oculus Optikgeräte GmbH, Wetzlar, Germany) to analyse and compare topometric, tomographic, pachymetric and Belin-Ambrósio Enhanced Ectasia Display III (BAD-D) data of both eyes of each patient. RESULTS: Most OI patients had type I disease (n = 24; 65%) but type III-VII patients were also included. Two patients had clinically overt bilateral keratoconus. OI patients had significantly higher maximum keratometry (45.2 ± 2.1 vs. 43.7 ± 1.2; p = 0.0416), front and back elevation (3.0 ± 3.3 vs. 2.1 ± 1.3, p = 0.0201; 11.1 ± 8.2 vs. 5.0 ± 3.7, p < 0.0001), index of surface variance (25.5 ± 13 vs. 17.4 ± 8.3; p = 0.0016), index of vertical asymmetry (0.21 ± 0.14 vs. 0.15 ± 0.06; p = 0.0215), index of height asymmetry (9.2 ± 14 vs. 6.0 ± 4.5; p = 0.0421), index of height decentration (0.02 ± 0.01 vs. 0.01 ± 0.01; p < 0.0001) and average pachymetric progression (1.01 ± 0.19 vs. 0.88 ± 0.14; p < 0.0001) readings. Thinnest corneal thickness and maximum Ambrósio relational thickness were significantly lower (477 ± 52 vs. 543 ± 26; 387 ± 95 vs. 509 ± 49; p < 0.0001). Two-thirds of OI patients had corneas with a minimum thickness < 500 µm. BAD-D value was significantly higher in OI patients (2.1 ± 1.4 vs. 0.9 ± 0.2; p < 0.0001). CONCLUSION: OI patients showed significant changes in corneal profiles compared with healthy subjects. A high proportion of patients had tomographically suspect corneas when using keratoconus diagnostic indices. Further studies are warranted to assess the true risk of corneal ectasia in OI patients.

Topical corticosteroids with topical cyclosporine A versus topical corticosteroids alone for immunological corneal graft rejection.

PURPOSE: To assess the efficacy and safety of supplementing topical cyclosporine A (CsA) to topical corticosteroids (CS), in the prophylaxis and treatment of corneal graft rejection following penetrating keratoplasty (PK). METHODS: Meta-analysis. Search was performed in PubMed, CENTRAL, ClinicalTrials.gov, reference lists of articles and conference proceedings. Primary outcomes: 1-year rejection-free survival rate (prophylaxis); resolution rate of rejection episodes (treatment). Secondary outcomes: 6- and 24-month rejection-free graft survival rate, number of rejection episodes during follow-up, time-to-resolution of rejection episode, 12- and 24-months graft survival rate, adverse events. Subgroup analyses were planned for high-risk grafts; primary vs. secondary prophylaxis of graft rejection episodes; and CsA concentrations of 0.05%, 1%, and 2%. RESULTS: Five studies of moderate methodological quality were included (one retrospective, four RCT), assessing 459 eyes (CS + CsA 226, CS 233). In the prophylaxis setting, supplemental CsA was associated with a higher rejection-free survival rate at 12-months (RR 1.25, 95% CI: 1.00-1.56, p = 0.05) and 24-months post-PK (RR 1.56, 95% CI: 1.15-2.11, p < 0.01), though no differences were found at the 6-months timepoint (p = 0.93). This effect was mostly verified using CsA 2% in the high-risk subset of patients. In the treatment setting, no differences were found in the resolution rate of rejection episodes (p = 0.23). No differences existed on drug-related adverse events. CONCLUSION: In the prophylaxis of rejection episodes post-PK, the combined regimen of CS + CsA was associated with a higher 1- and 2-year rejection-free graft survival rate. Subgroup analysis mostly supported the use of CsA 2% for high-risk grafts. Further studies are needed to validate these results.

Trabeculectomy with mitomycin C alone or coupled with intracamerular bevacizumab? A 2-year comparative study.

PURPOSE: To compare outcomes of primary trabeculectomy using either mitomycin C (MMC) alone versus MMC augmented with intracamerular bevacizumab in patients with open-angle glaucoma. METHODS: Retrospective, cohort, two-centre, comparative study. Patients' data were screened between October 2015 and March 2019, with inclusion requiring a minimum follow-up of 24 months. Primary outcome was intraocular pressure (IOP) lowering at 24 months, with surgical success defined with different maximum IOP targets (≤18, ≤16 and ≤14 mm Hg) and at least 30% reduction and higher than 5 mm Hg. Absolute success was achieved if no IOP-lowering medication was needed and a qualified success if otherwise. Safety outcomes were analysed. RESULTS: A total of 110 eyes underwent trabeculectomy with MMC, 51 of these combined with intracamerular bevacizumab. Both strategies were effective in terms of IOP lowering (baseline vs 2 years postoperatively: 24.4 (8.0) mm Hg vs 12.1 (5.3) mm Hg in the MMC group; 25.1 (8.7) vs 10.8 (3.8) mm Hg in the MMC+bevacizumab group; p<0.001 in both comparisons). The MMC+bevacizumab group had a significant difference towards higher efficacy on absolute success rates at all targets (IOP≤14 or ≤16 or ≤18 mm Hg; p=0.010, p=0.039 and p=0.007, respectively). The large majority (93%) of the MMC+bevacizumab group was drop-free at 24 months, and 41% had IOP below 10 mm Hg. Complication rates were low and similar between groups, with no systemic adverse events. CONCLUSIONS: Intracamerular bevacizumab in MMC-augmented primary trabeculectomy increases the chances of obtaining low IOP outcomes. This strategy may be useful when planning for surgeries aiming at target pressures in the low teens. TRIAL REGISTRATION NUMBER: ISRCTN93098069.

Characterization of posterior corneal astigmatism in a population with keratoconus.

Background: The curvature of the anterior corneal surface is traditionally used as a surrogate to estimate corneal astigmatism. In recent years, increasing importance has been attributed to posterior corneal astigmatism as an indicator. Our aim is to characterize the posterior corneal surface in a population with keratoconus and investigate its predictive value to keratoconus progression. Methods: Retrospective study from a tertiary care centre (Hospital de Santa Maria, Lisbon, Portugal). Eighty-five patients (85 eyes) with keratoconus were included. All patients had two tomographical examinations ≥12 months apart (Pentacam HR). Vector analysis was used to calculate anterior (ACA), posterior (PCA), and total corneal astigmatism (TCA). Multivariate logistic regression was used to assess the predictive value of PCA to keratoconus progression, adjusting for ACA, TCA and several tomographical indices. Results: Study participants had a mean age of 32 (SD = 12.5) years. Mean tomographical keratoconus classification was 2.16 (SD = 0.95), with a mean Kmax of 55.8D (SD = 7.8). Mean power of PCA, ACA and TCA was, respectively, -0.88D (SD = 0.84), 3.74D (SD = 2.36), and 3.06D (SD = 2.01) and its centroids were 0.44D x 15º, 1.65D x 112º, and 1.61D x 106º, respectively. The power of PCA was ≥0.50, 1.00 and 2.00D in 75.3%, 32.9%, and 3.5% of patients, respectively, inducing against-the-rule astigmatism in 60.0% of patients. On average, ACA overestimated TCA in 0.35D x 151º (p < .01). ACA and TCA were highly correlated but showed a lack of agreement for clinical purposes. A predictive role for PCA was excluded. Conclusions: In this population with keratoconus, PCA contributed substantially to TCA. However, PCA was not a valuable predictor for disease progression.

The effect of glaucoma treatment using high-intensity focused ultrasound on total and corneal astigmatism: a prospective multicentre study.

PURPOSE: Ultrasound cycloplasty (UCP) acts through the selective coagulation of the ciliary body using high-intensity focused ultrasound (HIFU) technology. The aim of this study was to investigate whether the application of ultrasound beams targeting the ciliary body using an external probe influences astigmatism. METHODS: Multicentre, prospective, single-arm, open-label study in adult patients with primary open-angle glaucoma and moderately uncontrolled intraocular pressure (IOP) under glaucoma medication. The primary outcome was induced corneal astigmatism, calculated from topography, and assessed statistically through vector analysis. Secondary outcomes included induced total astigmatism and mean changes from baseline in best-corrected visual acuity (logMAR) and IOP. Subgroup analysis was performed to assess the impact of device centring on corneal and total induced astigmatism. RESULTS: Fifty eyes were enrolled. Mean age was 69.6 ± 11.3 years. At 1, 3 and 6 months postprocedure, HIFU-induced corneal astigmatism was 0.88 D × 93°, 0.87 D × 106° and 1.16 D × 97°, respectively, while induced total astigmatism was 0.62 D × 103°, 0.42 × 106° and 0.39 × 107°. By the last follow-up, the percentage of patients with <0.50, <1.00, <1.50 and <2.00 D of induced corneal versus total astigmatism was 8.3% versus 46%, 29% versus 66%, 62.5% versus 88% and 79% versus 94%. Visual acuity was statistically significantly impaired at 1 month, but no difference remained by 3 and 6 months postprocedure. CONCLUSION: Ultrasound cycloplasty procedure is associated with increased corneal astigmatism. However, its impact on total refractive astigmatism is less pronounced.

Impact of laser iridotomy on headache symptoms in angle-closure subjects.

BACKGROUND: Migraine symptoms are frequently referred by glaucoma patients. Although most studies analyze headache in the acute setting of angle closure, many patients with chronic occludable angles also complain of headaches. The aim of this study was to determine the impact of laser peripheral iridotomy (LPI) on the magnitude and frequency of headache symptoms in patients with occludable angles. METHODS: Prospective cohort study. Patients with indication for prophylactic LPI due to occludable iridocorneal angle were included. Headache symptoms were assessed before and at least 4 weeks after LPI using the Headache Impact Test-6 (HIT-6) questionnaire. A HIT-6 score of ≥ 50 points was labeled as a clinically significant headache. RESULTS: Thirty-one subjects were included. Prophylactic LPI was performed in 60 eyes, as 2 patients were pseudophakic in the fellow eye. Baseline HIT-6 score was 59.9 ± 11.8, with over three quarters of these patients scoring higher than 50 points (n = 24). A statistically significant reduction in HIT-6 score was found after LPI treatment (45.4 ± 7.7, p < 0.01). Sub-analysis within the clinically symptomatic subjects disclosed a significant improvement after treatment in this group (baseline, 65.3 ± 6.2 vs post-LPI 46.2 ± 8.3, p < 0.01), with a high baseline HIT-6 score being predictive of a symptomatic improvement after LPI (χ2(8) = 15.3, p = 0.001). This is mimicked from the patient's perspective, as the two subjective questions after LPI, concerning pain intensity and frequency, report that 79.2% had a statistically significant improvement of the headaches. CONCLUSIONS: Within our sample, the majority of patients with occludable angles had clinically relevant headaches. LPI provided symptomatic relief in the majority of those patients with high HIT-6 scores. Further studies are needed to explore the relationships between headache and angle anatomy.

Complete ILM Peeling Versus Inverted Flap Technique for Macular Hole Surgery: A Meta-Analysis.

BACKGROUND AND OBJECTIVE: To compare complete internal limiting membrane (ILM) peeling with the inverted flap technique for macular hole (MH) surgery. PATIENTS AND METHODS: An electronic database search on PubMed, CENTRAL, and ClinicalTrials.gov was performed. Inclusion criteria were comparative prospective/retrospective studies including patients with MH of any size with at least 6 months of follow-up. The primary outcome was MH closure rate. Secondary outcomes were best-corrected visual acuity improvement and surgery-related adverse events. RESULTS: Sixteen papers enrolling 1,403 eyes were included (733 ILM peeling, 670 inverted flap). MH mean minimum diameter and time of symptomatic evolution were higher in the inverted flap group (531.1 µm ± 188.8 µm vs. 602.8 µm ± 223.8 µm; 10.4 ± 20.2 months vs. 12.0 ± 18.4 months; P < .01). Overall, MH closure rate was superior with the inverted flap technique (risk-ratio [RR]: 1.25; 95% confidence interval [CI], 1.14-1.38; P < .0001), as well as in all subgroups: idiopathic large MH (n = 362; RR: 1.12; 95% CI, 1.05-1.20; P < .001), myopic MH without retinal detachment (n = 133; RR: 1.35; 95% CI, 1.14-1.59; P < .001), and MH retinal detachment (n = 198; RR: 1.89; 95% CI, 1.31-2.73; P < .001). CONCLUSION: This meta-analysis suggests the inverted flap technique is more effective in achieving MH closure. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:187-195.].

Optic disc drusen in children: morphologic features using EDI-OCT.

AIMS: This study aimed to investigate morphologic features of optic disc drusen (ODD) and peripapillary hyperreflective ovoid mass-like structures (PHOMS) in children, using enhanced depth imaging optical coherence tomography (EDI-OCT). It also assessed if the presence of these features were associated with decreased peripapillary retinal nerve fibre layer (RNFL) thickness. METHODS: Retrospective observational study of children with ODD. All subjects underwent complete ophthalmic examination and multimodal imaging. ODD were identified on EDI-OCT as circumscribed hyporeflective spheroidal elements located in front of lamina cribrosa, fully or partially surrounded by a hyperreflective border. PHOMS were identified as hyperreflective ovoid structures located in the peripapillary circumference. Both associations between ODD and RNFL loss and PHOMS and RNFL loss were tested using chi-squared test. RESULTS: In total, 38 eyes of 20 children were analysed. PHOMS were present in 90% of patients. ODD and PHOMS were predominantly found in the nasal, superonasal and inferonasal sectors. A significant positive association was found between ODD and decreased RNFL thickness in the nasal (p = 0.02), superonasal (p = 0.05) and inferotemporal (p = 0.04) sectors. There was no significant association found with the presence of PHOMS. CONCLUSION: EDI-OCT allowed morphological analysis of ODD and PHOMS in children. Drusen were found to be distinct from PHOMS both in their appearance and impact on the RNFL. ODD are hyporeflective and appear on the ONH above the lamina cribrosa and were associated with decreased thickness of the RNFL. On the contrary, PHOMS are hyperreflective structures located around the ONH and were not associated with RNFL loss.

DMEK versus DSAEK for Fuchs' endothelial dystrophy: A meta-analysis.

PURPOSE:: To compare the safety and efficacy profiles of Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK) in adult patients with Fuchs' endothelial dystrophy. METHODS:: Electronic database search on MEDLINE and CENTRAL from inception to August 2017. We included all comparative studies of DMEK versus DSAEK in patients with diagnosed Fuchs' endothelial dystrophy. Studies assessing rescue procedures were excluded to minimize bias. Primary outcome: mean difference in best-corrected visual acuity (BCVA) at 3, 6, and 12 months postoperatively. Secondary outcomes: rates of graft primary failure, rejection, and rebubbling; other graft-related issues; mean difference in endothelial cell density; subjective visual outcomes; and patient satisfaction. RESULTS:: A total of 10 retrospective studies of moderate methodological quality were included (n = 947 eyes, 646 DMEK). BCVA was better with DMEK at all evaluated time points (0.16 logMAR at 12 months) comparing to DSAEK (0.30 logMAR; p < 0.001). DMEK had a 60% lower rate of rejection (risk ratio (RR) 0.4, 95% CI (0.24, 0.67), p = 0.0005), but required more rebubblings (RR = 2.48, 95% CI (1.32, 4.64), p = 0.005). DMEK had more primary graft failures and less endothelial cell density loss, but statistical difference was not reached. More patients were satisfied after DMEK (odds ratio = 10.29, 95% CI (3.55, 29.80), p < 0.0001). CONCLUSION:: DMEK showed better postoperative results regarding BCVA, patient satisfaction, and graft-related issues. However, the small number of studies with short follow-up times and other methodological issues prompt us to interpret these results carefully.

Glaucoma Gel Implant Learning Curve in a Teaching Tertiary Hospital.

PURPOSE: The XEN gel stent is a minimally invasive surgical device aimed at creating a subconjunctival drainage of aqueous humor, thereby reducing intraocular pressure (IOP). Being a novel device, doubts remain with regard to the efficacy and safety of its implantation in the early stage of new users. This paper illustrates the XEN implantation learning curve, assessed through several surgeons of different expertise. METHODS: This was a retrospective study on the first 6 XEN implants performed by each of the 10 certified ophthalmic surgeons. Simultaneous cataract surgery was allowed (phaco-XEN). Primary outcomes were as follows: surgical time; intraoperative and postoperative surgical complications. Secondary outcomes were as follows: IOP; the number of topical drugs in use; the need for needling procedures. Outcome data were collected preoperatively and at postoperative days 1, 7, 15, 30, 60, and 90. Statistical analysis was performed with STATA 14.1 and SPSS. RESULTS: Sixty patients were included (56.7% female patients). Mean age was 73 years (45 to 89). Mean preoperative IOP was 23.8±8.95 mm Hg. From the included patients, 29 (48.3%) were submitted to simple XEN implant and 31 (51.7%) to phaco-XEN. In both groups, mean surgical time decreased by 9 minutes throughout the 6-implant learning curve. Final IOP was 15±7.27 mm Hg in the stent group (-43% than baseline), and 14.92±3.32 mm Hg in the phaco-XEN group (-16% than baseline). On average, patients decreased 2 topical IOP-lowering drugs. Needling procedures were performed in 17 patients (28.3%). CONCLUSIONS: XEN gel stent was associated with a fast learning curve, by both experienced surgeons and novice residents. By the sixth implant, both groups had considerably decreased mean surgical time and complication rates.

Sulfur Hexafluoride 20% Versus Air 100% for Anterior Chamber Tamponade in DMEK: A Meta-Analysis.

PURPOSE: To compare intracameral 20% sulfur hexafluoride (SF6) versus 100% air as tamponade for graft attachment in Descemet membrane endothelial keratoplasty (DMEK). METHODS: Using an electronic database search on MEDLINE and CENTRAL from inception to December 2017, we performed a literature review and meta-analysis including all comparative studies of SF6 at a 20% concentration (20% SF6) versus pure air (100% air) for anterior chamber tamponade in DMEK. The primary outcome was the rebubbling rate at the final observation. The secondary outcomes were 1) the graft detachment rate, 2) mean difference (MD) in best-corrected visual acuity (BCVA), 3) manifest refraction spherical equivalent, 4) central corneal thickness (CCT), 5) percentage of endothelial cell loss (ECL), and 6) rate of pupillary block by the final observation. Statistical analysis was performed using RevMan5.3 software. RESULTS: Five retrospective studies were included, assessing 1195 eyes (SF6 277; air 918). The main indication for surgery was Fuchs endothelial dystrophy (SF6 85.2%; air 86.2%) and bullous keratopathy (SF6 10.8%; air 10.0%). Overall, studies were of moderate to good methodological quality. Patients in the SF6 group required 58% less rebubbling procedures (risk ratio 0.42, 95% confidence interval (CI), 0.31-0.56, P < 0.0001). No differences were found regarding BCVA improvement (MD 0.03, 95% CI, -0.05 to 0.11, P = 0.49). SF6 was associated with a minor hyperopic shift (MD 0.37 D, 95% CI, -0.95 to -0.21, P = 0.21). No differences were found regarding CCT, ECL, and rate of pupillary block (P > 0.05). CONCLUSIONS: In DMEK, 20% SF6 tamponade and longer postoperative time supine were associated with 58% fewer rebubbling procedures, and an ECL not statistically different from using 100% air.