Endothelin-1 Plasma and Aqueous Humor Levels in Different Types of Glaucoma: A Systematic Review and Meta-Analysis.

Background and Objectives: Several studies suggest the complex relationship between Endothelin-1 (ET-1) levels with various types of glaucoma. This systematic review and meta-analysis explore ET-1 levels in plasma and aqueous humor among different types of glaucoma. Materials and Methods: A literature search (PubMed, ScienceDirect, Cochrane Library) was made up to April 2024 (PROSPERO: CRD42023430471). The results were synthesized according to PRISMA Guidelines. Results were presented as standardized mean differences (SMD) with 95% confidence intervals (CI). Results: A total of 2597 subjects (1513 patients with glaucoma vs. 1084 healthy controls) from 23 studies were included in a meta-analysis. Notably, patients with glaucoma reported significantly higher plasma levels of ET-1 compared to controls (SMD: 1.21, 95% CI: 0.59-1.82, p < 0.001). Particularly, plasma ET-1 levels were higher in primary open-angle glaucoma (POAG) (SMD: 0.87, 95% CI: 0.09-1.65, p < 0.05), normal-tension glaucoma (SMD: 0.86, 95% CI: 0.27-1.46, p = 0.05), and angle-closure glaucoma patients (SMD: 1.03, 95% CI: 0.43-1.63, p < 0.001) compared to healthy controls. Moreover, ET-1 aqueous humor levels were significantly higher in patients with glaucoma compared to controls (SMD: 1.60, 95% CI: 1.04-2.15, p < 0.001). In particular, aqueous humor levels were higher in POAG patients (SMD: 2.03 95% CI: 1.00-3.14, p < 0.001), and pseudoexfoliative glaucoma patients (SMD: 2.03, 95% CI: 1.00-3.07, p < 0.001) compared to controls. Conclusions: This meta-analysis indicates that elevated levels of ET-1 plasma and aqueous humor are significantly associated with different types of glaucoma. The pathogenesis of ET-1-related mechanisms may vary across different glaucoma types, indicating that possible therapeutic approaches targeting ET-1 pathways should be tailored to each specific glaucoma type.

Corneal Irregularity Induced by Transepithelial Photorefractive Keratectomy in a Patient With Partial Limbal Stem Cell Deficiency.

PURPOSE: The aim of this study was to present a case of transepithelial photorefractive keratectomy (trans-PRK) laser ablation in a patient with partial limbal stem cell deficiency (LSCD) that resulted in corneal irregularity. METHODS: A 23-year-old man with bilateral partial LSCD underwent trans-PRK for myopia correction 2 months before presentation to our department. Trans-PRK ablation was performed with a phototherapeutic keratectomy ablation profile set at 60 µm in the OD and 57 µm in the OS and 8 mm zone. At the time of presentation, the patient complained of decreased visual acuity. Corrected distant visual acuity was 20/20 (-3.25, -0.75 × 180 degrees) and 20/50 (-3.00, -3.00 × 180 degrees) in the OD and the OS, respectively. No further ocular history was reported other than prolonged soft contact lens use for myopia. Pre-trans-PRK tomography (WaveLight Oculyzer II diagnostic system, WaveLight GmbH, Germany) revealed bilateral superior steepening with corresponding epithelial thinning as obtained by the epithelial map using Optovue optical coherence tomography (Visionix Luneau technology). Slit-lamp examination showed bilateral superficial neovascularization, suggestive of early-stage LSCD. RESULTS: A nonuniform laser stromal ablation resulting in corneal irregularity and decreased visual acuity was observed 2 months postoperatively. During the 6-month follow-up, corneal tomography was stable with only minimal improvement. At that time, corrected distant visual acuity remained 20/20 (-2.75, -0.75 × 160 degrees) in the OD and 20/50 (-3.00, -3.00 × 180 degrees) in the OS. CONCLUSIONS: Trans-PRK seems to be a contraindication in cases with corneal epithelial irregularities and could lead to abnormal and nonuniform stromal ablation .

Three-Year Results of Simultaneous Transepithelial Phototherapeutic Keratectomy and Conventional Photorefractive Keratectomy (Cretan Protocol Plus) Followed by Corneal Crosslinking for Keratoconus.

PURPOSE: The aim of this study was to present the 3-year outcomes after simultaneous transepithelial phototherapeutic keratectomy (t-PTK) and conventional photorefractive keratectomy (PRK) followed by corneal crosslinking (CXL) for keratoconus. METHODS: In this prospective, interventional case series, patients with progressive keratoconus underwent simultaneous t-PTK and conventional PRK followed by CXL (Cretan protocol plus). Visual, refractive, and topographic outcomes were evaluated along with endothelial cell density (ECD) preoperatively and at 1, 2, and 3 years postoperatively. RESULTS: Twenty-two patients (31 eyes) were enrolled. No intraoperative or postoperative complications were observed in any of the patients. Logarithm of the minimum angle of resolution (logMAR) mean uncorrected and mean corrected distance visual acuity improved from 0.81 ± 0.40 and 0.18 ± 0.21 preoperatively to 0.38 ± 0.33 ( P < 0.001) and 0.06 ± 0.12 ( P < 0.001) at 3-year follow-up. Mean spherical equivalent improved from -5.39 ± 3.89 diopters (D) preoperatively to -2.29 ± 2.65 D ( P < 0.001) at 3 years postoperatively. Mean corneal astigmatism reduced from -4.70 ± 2.86 D preoperatively to -3.55 ± 2.45 D ( P = 0.001) at 3 years postoperatively. No ECD alterations were observed throughout the 3-year follow-up ( P > 0.05). CONCLUSIONS: Simultaneous t-PTK and conventional PRK followed by CXL seems to be an effective and safe treatment for progressive keratoconus over 3-year follow-up.

"Corneal Plication" for the Management of Progressive Corneal Graft Protrusion in Patients With Keratoconus: a New Technique.

PURPOSE: The purpose of this study was to present a new surgical technique, namely corneal plication, for the management of high astigmatism and progressive corneal graft protrusion after penetrating keratoplasty (PKP) for keratoconus. METHODS: New surgical approach description. RESULTS: A 61-year-old woman with a history of bilateral keratoconus was referred to our institute for the management of progressive corneal graft protrusion in her left eye 25 years after PKP. On presentation, the uncorrected distance visual acuity in the involved eye was counting fingers, whereas slit-lamp examination revealed a clear graft with a crescentic area of thinning in the inferior host cornea, extending from 4 to 9 o'clock that resulted in significant graft protrusion and astigmatism. We proceeded with a novel surgical approach that included "folding" and suturing the thinned, diseased corneal tissue and thus creating a form of corneal plication. No intraoperative or postoperative complications were observed, and uncorrected distance visual acuity was 0.32 6 months after the operation. CONCLUSIONS: Corneal graft plication may represent a realistic alternative to more invasive procedures, currently used for the management of this long-term post-PKP complication in patients with keratoconus because it is a nonperforating technique that seems to provide satisfactory anatomical and visual outcomes without the need for any tissue excision or regrafting.

Evolution of corneal flattening after repeated corneal cross-linking during a 6-year follow-up.

PURPOSE: To report the evolution of corneal flattening after repeated corneal cross-linking (CXL) in a patient with progressive keratoconus during a 6-year follow-up. METHODS: Case report. RESULTS: A 27-year-old female underwent CXL for progressive keratoconus. Postoperatively, corneal topography revealed keratoconus progression with an increase of 1.20 diopters (D) in maximum keratometry (Kmax) and CXL was repeated. After the second treatment, a continuing significant corneal flattening (up to 16.00 D in Kmax) was observed during the first 5 years followed by stabilization during the last sixth year of follow-up. Both uncorrected and corrected distance visual acuity were improved while corneal thickness was decreased. There were no complications such as corneal opacification or endothelial cells decrease during the follow-up period. CONCLUSION: Repeated CXL can induce an excessive corneal flattening more pronounced during the first years of follow-up followed by stabilization thereafter.

Combined Astigmatic Arcuate Keratotomy with Descemet Automated Endothelial Keratoplasty.

We report the results of simultaneous astigmatic arcuate keratotomy (AK) and Descemet automated endothelial keratoplasty (DSAEK). A 55-year-old patient with a history of high myopia was referred for the management of bullous keratopathy secondary to an anterior chamber phakic intraocular lens (pIOL). IOL explantation through a 5.5-mm corneal incision, cataract extraction, and posterior chamber IOL implantation, combined with DSAEK, were performed. Postoperatively, increased astigmatism up to 2.0 diopters (Dpt) was observed, attributed to the large corneal incision, and remained stable, despite suture removal at 3 months. One year postoperatively, the graft showed signs of progressive endothelial dysfunction. A combined procedure of astigmatic AK and DSAEK was thus performed. After 6 months, topographic astigmatism was significantly reduced to 0.5 Dpt and best-corrected visual acuity increased. In conclusion, simultaneous astigmatic AK and DSAEK could be an effective combination for treating patients with well-documented pre-existing astigmatism and endothelial decompensation.

Intraocular Lens Refractive Index and Its Impact on External Surface Reflections.

PURPOSE: To determine and compare the origin of the external surface reflections produced by commonly used intraocular lenses (IOLs). METHODS: The specular reflection taking place at the anterior surface of eight types of IOLs (IOL power = 22.00 diopters [D]) with different refractive indices (RIs), optical design, and ultraviolet and blue light-filtering function were measured. The experimental set-up included a laser beam light source (3.5 mW, 532 nm) and a saline-filled model eye containing the IOL to be examined. External surface reflections were measured using a power meter, and the IOL surface reflectance (%) was compared among the eight IOLs investigated. RESULTS: External reflections from the anterior surface of the studied implants increased as the RI of the IOL material increased. The IOL models composed of high RI material (RI = 1.56 ± 0.02) were found to have a more than threefold higher external surface reflections compared to those with low RI (RI = 1.45 ± 0.02). Ultraviolet or blue light-filtering functions showed no significant correlation with the external reflectance. CONCLUSIONS: IOLs with a high RI are associated with external surface reflections that are more than threefold higher than those with lower RI. The "cat's eye" phenomenon seen in pseudophakic eyes by an outside observer strongly depends on the RI, but is independent of the filter incorporated in the IOL. [J Refract Surg. 2021;37(6):398-402.].

Small incision lenticule extraction retreatment in a patient with high residual refractive error after photorefractive keratectomy: A case report.

A 36-year-old male underwent uneventful small incision lenticule extraction (SMILE) for the correction of his high residual refractive error 12 years after photorefractive keratectomy (PRK). Preoperatively, uncorrected distance visual acuity (UDVA) was counting fingers in both eyes. Corrected distance visual acuity was 20/20 in the right and 20/30 in the left eye due to amblyopia. One month after SMILE, UDVA was 20/20 and 20/30 in the right and left eye, respectively; post-PRK corneal haze had reduced. During the 4-year follow-up, UDVA remained stable and there were no complications. SMILE could be a good alternative approach for retreatment in post-PRK patient.

Corneal cross-linking (CXL) combined with refractive surgery for the comprehensive management of keratoconus: CXL plus.

The past two decades have witnessed an unprecedented evolution in the management of keratoconus that demands a holistic approach comprising of inhibiting the ectatic progression as well as visual rehabilitation. The advent of corneal cross-linking (CXL) in the late 1990s resulted in long-term stabilization of the ectatic cornea along with limited reduction in corneal steepening and regularization of corneal curvature. However, CXL as a standalone procedure does not suffice in rehabilitating the functional vision especially in patients who are unwilling or intolerant towards contact lenses. The concept of "CXL plus" was proposed which incorporates adjunctive use of refractive procedures with CXL in order to overcome the optical inefficiency due to corneal irregularity, decrease the irregular astigmatism, correct the residual refractive error and improve functional visual outcome in keratoconus. Several refractive procedures such as conductive keratoplasty (CK), photorefractive keratectomy (PRK), transepithelial phototherapeutic keratectomy (t-PTK), intrastromal corneal ring segments (ICRS) implantation, phakic intraocular lens (PIOL) implantation and multiple other techniques have been combined with CXL to optimize and enhance the CXL outcome. This review aimed to summarize the different protocols of CXL plus, provide guidelines for selection of the optimum CXL plus technique and aid in decision-making for the comprehensive management of cases with primary keratoconus in addition to discussing the future and scope for innovations in the existing treatment protocols.

Accuracy of dynamic contour tonometry, Goldmann applanation tonometry, and Tono-Pen XL in edematous corneas.

PURPOSE: To investigate in vitro the accuracy of dynamic contour tonometry, Goldmann applanation tonometry, and Tono-Pen XL in edematous corneas. METHODS: Experimental study included 20 freshly enucleated porcine eyes. Epithelium was debrided, and eyes were divided in four groups. Groups were immersed in 35%, 40%, 50%, and 60% glycerin solutions for 3 hours. Subsequently, globes were mounted in a special holder, and their intraocular pressure was hydrostatically adjusted. Intraocular pressure was measured by means of dynamic contour tonometry, Goldmann applanation tonometry, and Tono-Pen XL while adjusting true intraocular pressure to 17, 33, and 50 mm Hg. Ultrasound pachymetry was performed. RESULTS: Mean corneal thickness was 914.5 ± 33.3 µm (730-1015 µm). In true intraocular pressure of 33 mm Hg, Goldmann applanation tonometry and dynamic contour tonometry significantly underestimated true intraocular pressure (mean Goldmann applanation tonometry: 14.7 ± 4.8 mm Hg, p < 0.001, mean dynamic contour tonometry: 21.6 ± 6.8, p < 0.001). Tono-Pen XL also underestimated, but difference was not statistically significant (Tono-Pen XL: 27.9 ± 9.7, p = 0.064). In true intraocular pressure of 50 mm Hg, all three methods significantly underestimated (Goldmann applanation tonometry: 17.6 ± 5.3 mm Hg, p < 0.001, dynamic contour tonometry: 26.8 ± 6.3 mm Hg, p < 0.001, Tono-Pen XL: 35.6 ± 8.4 mm Hg, p < 0.001). The error in measured intraocular pressure for each method (true minus measured intraocular pressure) was significantly correlated to true intraocular pressure (p < 0.001). The intraocular pressure measurements of each eye taken under true intraocular pressure of 17 and 33 mm Hg with the three methods were correlated to each other. Measurements taken under intraocular pressure of 50 mmHg were not correlated to each other. Corneal thickness was not correlated to intraocular pressure measurement. CONCLUSION: Goldmann applanation tonometry, dynamic contour tonometry, and Tono-Pen XL underestimate intraocular pressure when measured under edematous conditions. Tono-Pen XL showed better accuracy, especially in lower true intraocular pressure. The measurement error increases when true intraocular pressure increases in all three methods.

A New Surgical Approach for the Management of Acute Corneal Hydrops Complicated With Corneal Perforation.

PURPOSE: To report an unusual case of a patient with keratoconus and acute hydrops complicated with corneal perforation and describe its management using a new surgical approach. METHODS: A case report and new surgical approach description. RESULTS: A 47-year-old female patient with a history of keratoconus and implantable contact lens surgery presented at our institute with symptoms of acute corneal hydrops in her right eye. On examination, best corrected visual acuity was of counting fingers in the involved eye. Slit-lamp examination revealed a small inferotemporal corneal perforation, surrounded by marked corneal edema and a positive Seidel test. Initial attempts of conservative treatment with cyanoacrylate tissue adhesive application and bandage soft contact lens placement were ineffective. We decided to proceed with an inferior, lamellar wedge resection of the diseased corneal tissue. One month postoperatively, the cornea remained clear, whereas best corrected visual acuity was 0.1. CONCLUSIONS: Lamellar wedge resection could represent an alternative surgical approach for keratoconic patients, with eccentric acute hydrops and subsequent corneal perforation that provides rapid visual rehabilitation.

Simultaneous Penetrating Keratoplasty and Implantation of a New Scleral-Fixated, Sutureless, Posterior Chamber Intraocular Lens (Soleko, Carlevale): A Novel Technique.

PURPOSE: To describe a novel technique of combined penetrating keratoplasty (PKP) with implantation of a new scleral-fixated, sutureless, posterior chamber intraocular lens (PC-IOL) (Soleko, Carlevale). METHODS: New surgical approach description. RESULTS: We describe a novel technique for the management of PKP graft failure and posttraumatic aphakia with repeat-PKP and simultaneous implantation of a new scleral-fixated, sutureless PC-IOL. The postoperative course was uneventful, and the patient reported marked improvement in his vision. Up to 6 months postoperatively, the graft showed no signs of failure or rejection, the intraocular lens remained well-positioned, and no complications were observed. CONCLUSIONS: The favorable final outcome of our patient suggests that simultaneous PKP and implantation of this new scleral-fixated, sutureless PC-IOL may represent an efficient and effective method for the management of aphakia combined with corneal scarring.

Burr-Assisted Anterior Lamellar Keratoplasty (DALK) in Patients with Corneal Stromal Scarring: A Case Series.

PURPOSE: To describe a modified technique of deep anterior lamellar keratoplasty (DALK) assisted by diamond ophthalmic burr (DOB) in two patients with corneal stromal scarring. METHODS: Two patients with corneal stromal scarring underwent a modified DALK technique with corneal stromal polishing assisted by a DOB until the level of the Descemet membrane. RESULTS: There were no intra- or postoperative complications. Six months postoperatively, the corneal graft was clear, while corrected distance visual acuity improved in both cases. CONCLUSIONS: Burr-assisted DALK seems to represent an alternative surgical technique in patients with corneal stromal scarring.

Surgical management of post-Descemet stripping automated endothelial keratoplasty interface haze associated with interface deposits.

We describe an effective technique for the management of graft-host interface haze associated with interface deposits after Descemet-stripping automated endothelial keratoplasty (DSAEK) with bimanual irrigation/aspiration. A Tan marginal dissector was used to separate the graft from the stroma in the nasal two-thirds of the graft-host interface. The aspiration handpiece was inserted in the interface through the nasal side-port corneal incision and a separate irrigation tip was placed in the anterior chamber (AC) through the temporal corneal paracentesis. Meticulous rinsing of the two-thirds of the interface area and the AC was performed. At the end of the procedure, air was injected into the AC to float the donor graft against the host stromal bed and facilitate graft adherence. Postoperative anterior segment optical coherence tomography and slit-lamp examination confirmed elimination of the interface haze-deposits and a well-attached graft. An improvement in visual acuity was noted.

Using corneal graft from keratoconic donor for lamellar and penetrating keratoplasties.

We report the use of two corneal grafts derived from a donor, with a history of early stage keratoconus, for lamellar and penetrating keratoplasty. The first graft was used to perform Descemet stripping automated endothelial keratoplasty (DSAEK) in a patient with endothelial dysfunction and advanced pseudoexfoliative glaucoma. The second graft was used for an emergency penetrating keratoplasty in a patient with corneal perforation secondary to uncontrolled herpes keratitis. In the first case, 1 year postoperatively, the graft was clear and attached with no signs of rejection or failure. In the second case, the perforation did not relapse after keratoplasty and the globe retained its structural integrity during the 1-year follow-up.

Femtosecond-Assisted Elliptical LASIK Flap for the Correction of Post-Arcuate Keratotomy Residual Astigmatism.

We report the application of an elliptical femtosecond laser-assisted in situ keratomileusis (LASIK) flap for the management of post-arcuate keratotomy (AK) residual astigmatism. An 82-year-old male was referred to our institute for evaluation of his right eye due to residual regular astigmatism 1 year after AK. On examination, uncorrected distance visual acuity (UDVA) was 20/50 and corrected distance visual acuity was 20/25 (+3.25 -5.50 × 125). Slit-lamp examination revealed two 70-arc length peripheral corneal incisions at the 7.50-mm zone. The patient underwent femtosecond-assisted LASIK for the correction of residual astigmatism. An elliptical LASIK flap was adjusted intraoperatively with a 2-dimension diameter of 7.98 × 6.69 mm in order to avoid intersection of the flap with the AK incisions. The short flap diameter was placed along the meridian of the incisions and the long diameter in the perpendicular meridian, corresponding to the excimer laser astigmatic ablation pattern. No intraoperative or postoperative complications were encountered. Six months postoperatively, UDVA improved to 20/25 with a manifest refraction of pl -0.75 × 5. No AK incision flap-related complications were observed.

Predictors of Visual Acuity Improvement and Supernormal Vision After Refined Single-Step Transepithelial Photorefractive Keratectomy.

PURPOSE: To investigate predicting factors of visual acuity improvement and achieving uncorrected (UDVA) or corrected (CDVA) distance visual acuity supernormal vision (⩾ 15/10; Snellen 20/13) 1 year after refined transepithelial photorefractive keratectomy (TransPRK). METHODS: In this retrospective case series, a total of 155 eyes with myopia (mean ± standard deviation = -3.53 ± 1.81 diopters) with and without astigmatism (range = 0.25 to 4.50 diopters) were recruited and observed for 1 year. Patients underwent refined single-step TransPRK using the SCHWIND AMARIS 500 laser (SCHWIND eye-tech-solutions GmbH, Kleinostheim, Germany). The main predicting factors of postoperative supernormal vision and visual acuity improvements were sought by statistical modeling. RESULTS: Logistic models showed mesopic contrast sensitivity, high laser fluence, and coma higher-order aberration (HOA) as predicting factors for both UDVA and CDVA super-normal vision. Myopia, astigmatism, dynamic cyclotorsion correction, optical zone, and transitional zone showed associations only in simple models and were not retained in multivariable models. According to the linear regression models, CDVA, mesopic contrast sensitivity, coma HOA, and keratometry were common predictors of both postoperative UDVA and CDVA improvement compared to preoperative UDVA. Astigmatism, optical and transitional zones, and high laser fluence were common predictors only in simple regression models. CONCLUSIONS: Through statistical modeling, preoperative CDVA, mesopic contrast sensitivity, coma HOA, and simulated keratometry were found to be the main factors that predicted improvement of both postoperative CDVA and UDVA compared to preoperative CDVA. Furthermore, mesopic contrast sensitivity, coma HOA, and high laser fluence were the common predictors of achieving both CDVA and UDVA supernormal vision 1 year after refined single-step TransPRK. [J Refract Surg. 2019;35(12):771-780.].

Occult Spontaneous Ocular Perforation Presenting as Conjunctival Chemosis in a Patient with Marfan's Syndrome.

We report a case of occult spontaneous ocular perforation presenting as conjunctival chemosis in a patient with Marfan's syndrome (MFS). A 38-year-old female with MFS presented with bilateral conjunctival chemosis since 6 months. Best-corrected visual acuity was 20/20 in both eyes. On slit-lamp examination, a diffuse conjunctival chemosis was observed in both eyes without any signs of ocular hypotony (decreased visual acuity, low intraocular pressure, shallow anterior chamber, pupil distortion, hypotony maculopathy, and chorioretinal folds). Anterior-segment optical coherence tomography revealed a corneoscleral fistula at the left nasal limbus, without any similar finding in the right eye. A scleral patch was performed at the site of the perforation. At 3 month's follow-up, the left chemosis had regressed, with a stable best-corrected visual acuity in both eyes. However, on ultrasound biomicroscopy, another fistula at the right superior limbus was found, and the patient was referred for treatment with a scleral patch. In conclusion, conjunctival chemosis in a patient with MFS should raise the suspicion of an occult spontaneous ocular perforation.