Glaucoma is an insidious group of eye diseases causing degeneration of the optic nerve, progressive loss of vision, and irreversible blindness. The number of people affected by glaucoma is estimated ...at 80 million in 2021, with 3.5% prevalence in people aged 40–80. The main biomarker and risk factor for the onset and progression of glaucoma is the elevation of intraocular pressure. However, when glaucoma is diagnosed, the level of retinal ganglion cell death usually amounts to 30–40%; hence, the urgent need for its early diagnosis. Molecular biomarkers of glaucoma, from proteins to metabolites, may be helpful as indicators of pathogenic processes observed during the disease’s onset. The discovery of human glaucoma biomarkers is hampered by major limitations, including whether medications are influencing the expression of molecules in bodily fluids, or whether tests to validate glaucoma biomarker candidates should include human subjects with different types and stages of the disease, as well as patients with other ocular and neurodegenerative diseases. Moreover, the proper selection of the biofluid or tissue, as well as the analytical platform, should be mandatory. In this review, we have summarized current knowledge concerning proteomics- and metabolomics-based glaucoma biomarkers, with specificity to human eye tissue and fluid, as well the analytical approach and the main results obtained. The complex data published to date, which include at least 458 different molecules altered in human glaucoma, merit a new, integrative approach allowing for future diagnostic tests based on the absolute quantification of local and/or systemic biomarkers of glaucoma.
To investigate the middle-term intraocular pressure (IOP) results after implantation of a posterior chamber collagen copolymer phakic intraocular lens (IOL) (V4c Visian; STAAR Surgical Co., Nidau, ...Switzerland) with a central hole in patients with myopia.
This retrospective study enrolled patients who had implantation of a phakic IOL with a central hole. IOP, central vault, and adverse events were evaluated 1, 3, 6, 12, and 24 months postoperatively.
The study enrolled 763 eyes (384 patients, 128 men and 256 women). Mean follow-up was 7.0 ± 7.2 months (range: 1 to 24 months). The mean IOP was 13.2 ± 2.1 mm Hg preoperatively. Postoperatively, the mean IOP was 12.4 ± 1.7 mm Hg at 1 month, 12.5 ± 1.8 mm Hg at 3 months, 12.6 ± 1.3 mm Hg at 6 months, 12.6 ± 1.4 mm Hg at 12 months, and 12.7 ± 1.1 mm Hg at 24 months. Only one case (0.13%) presented an increased IOP (> 21 mm Hg) during the observation period. No pupillary block or acute angle closure was recorded. IOP at the final follow-up visit was 12.8 ± 1.3 mm Hg.
Implantation of central hole phakic IOL in myopic patients provided good and safe IOP outcomes throughout the 24-month observation period. J Refract Surg. 2017;33(4):244-249..
To compare the clinical outcomes in femtosecond laser–assisted deep anterior lamellar keratoplasty (F-DALK) to manual non-laser deep anterior lamellar keratoplasty (M-DALK) for keratoconus in a ...multi-surgeon public healthcare setting.
Single-center, comparative, retrospective interventional case series.
Population: Consecutive cases of keratoconus treated with big-bubble F-DALK from August 1, 2015, to September 1, 2018 and big-bubble M-DALK from September 1, 2012, to September 30, 2016. Setting: Moorfields Eye Hospital, London. Observations: Data on preoperative status, operative details, intraoperative and postoperative complications, secondary interventions, and visual outcomes were archived on a customized spreadsheet for analysis. MainOutcomeMeasures: Rate of intraoperative perforation and conversion to penetrating keratoplasty (PK) and the percentage of patients, post removal of sutures (ROS), with corrected distance visual acuity (CDVA) ≥20/40.
We analyzed 58 eyes of 55 patients who underwent F-DALK and 326 eyes of 309 patients who underwent M-DALK. Intraoperative perforation of Descemet membrane occurred in 15 of 58 (25.9%) F-DALK cases compared to 148 of 326 (45.4%) M-DALK cases (P = .006). Intraoperative conversion to PK was carried out in 2 of 58 (3.4%) F-DALK cases compared to 80 of 326 (24.5%) M-DALK cases (P = .001). Post ROS, 86.5% of F-DALK eyes had a CDVA of ≥20/40 (15 ± 7.3 months after surgery) compared to 83.7% of M-DALK eyes (24.9 ± 10.6 months) (P = .825).
Laser automation of some steps in DALK for keratoconus may reduce the rate of intraoperative Descemet perforation and the conversion to PK in a multi-surgeon setting.
Keratoconus is a heterogeneous disease associated with a range of pathologies, including disorders that involve proteoglycans (PGs). Some PG alterations, mainly in keratan sulfate (KS), occur in ...keratoconus. In this article, we studied the differential expression of the genes encoding PGs in cells isolated from keratoconus patients and healthy controls, as well as in corneal sections.
Human central corneal tissue was obtained from cadaver donors and patients undergoing penetrating keratoplasty surgery. A transcriptomic approach was used, employing quantitative PCR, to analyze both the expression of the enzymes involved in glycosaminoglycan (GAG) biosynthesis and the PG core proteins. The expressions of the differentially expressed core proteins and of the GAG chains were also analyzed by immunocytochemistry in the cultured cells, as well as by immunohistochemistry in corneal sections.
The mRNA levels of most major matrix PG mRNAs in the cultured keratoconic stromal cells decreased except collagen XVIII, which increased. At keratocyte surfaces, some heparan sulfate PGs were down-regulated. With respect to GAGs, there were changes in gene expression for the polymerization of the GAG chains, mainly KS and chondroitin sulfate, and in the modification of the saccharidic chains, pointing to an alteration of the sulfation patterns of all GAG species.
Most of the PG core proteins underwent significant changes in cultured keratoconic cells and corneas. With regard to GAG chains, the polymerization of the chains and their chemical modification was modified in way that depended on the specific type of GAG involved.
To examine clinical outcomes in deep anterior lamellar keratoplasty (DALK) for keratoconus using contemporary techniques in a multisurgeon public healthcare setting.
Consecutive, retrospective case ...series.
Setting: Moorfields Eye Hospital, London, United Kingdom. Study Population: Consecutive cases of keratoconus treated with non–laser assisted DALK from September 1, 2012, to September 31, 2016. Observation Procedure: Data on preoperative status, operative details, intraoperative and postoperative complications, secondary interventions, and visual outcomes were archived for analysis. Main Outcome Measures: Graft failure rate and percentage of patients with corrected distance visual acuity (CDVA) ≥20/40 within 1 year of surgery and at final review after suture removal.
Three hundred fifty-seven eyes of 338 patients undergoing DALK (91.3% big-bubble technique attempted) were analyzed. A total of 4.2% (95% confidence interval CI 2.4%–6.8%) of corneal transplants had failed within the follow-up period (21.8 ± 11.4 months), and 75.9% of eyes had CDVA ≥20/40 within 1 year of surgery, rising to 81% after suture removal. Forty-two primary surgeons (31 trainees) participated. Intraoperative perforation of Descemet membrane occurred in 45.4% of eyes. A total of 24.1% were converted to penetrating keratoplasty (PK) intraoperatively. Conversion to PK increased the risk of transplant rejection (P = .026; odds ratio OR 1.94; 95% CI 1.1–3.5) and secondary glaucoma (P = .016; OR 4.0; 95% CI 1.3–12.4). Transplant rejection increased the risk of graft failure both overall (P = .017; OR = 3.9; 95% CI 1.4–11.0) and when cases converted to PK were excluded (P = .028; OR = 3.35; 95% CI 1.1–9.9).
DALK for keratoconus achieves early results similar to those published for PK in a multisurgeon setting. Conservative management of intraoperative Descemet membrane perforation, where possible, may be safer than conversion to PK.
To evaluate the efficacy, safety, predictability, and stability of sequential Ferrara intrastromal corneal ring segment (ICRS) and intraocular lens (IOL) implantation in patients with keratoconus and ...cataract.
Fernández-Vega Ophthalmological Institute, Oviedo, Spain.
Retrospective case series.
This study comprised patients with keratoconus and cataract who had ICRS implantation followed 6 months later by IOL implantation. The uncorrected (UDVA) and corrected (CDVA) distance visual acuities and residual refractive errors, analyzed using vector analysis, were recorded preoperatively, 6 months after ICRS implantation, 6 months after IOL implantation, and 3 years and 5 years thereafter.
Seventy eyes of 47 patients were studied. The mean UDVA was 1.08 logMAR ± 0.24 (SD) preoperatively, 0.95 ± 0.31 logMAR 6 months after ICRS implantation (P = .03), and 0.44 ± 0.29 logMAR 6 months after IOL implantation (P < .0001). The mean CDVA changed from 0.35 ± 0.23 logMAR before surgery to 0.28 ± 0.22 logMAR 6 months after ICRS implantation (P < .0001) and to 0.11 ± 0.16 logMAR 6 months after IOL implantation (P < .0001). The UDVA and CDVA were stable over the period after the second procedure (P > .05). The spherical equivalent (SE) and the refractive cylinder declined steeply after IOL implantation (P < .001) and then were stable (P > .05).
Sequential ICRS and IOL implantation provided good visual and refractive outcomes and was an effective, safe, predictable, and stable procedure for the treatment of patients with keratoconus and cataract.
To assess the long-term correction of moderate to high myopia using a posterior chamber phakic intraocular lens with a central port design.
Uncorrected (UDVA) and corrected (CDVA) distance visual ...acuities, refraction, intraocular pressure (IOP), endothelial cell density (ECD), vault, and adverse events over a 5-year period were evaluated retrospectively.
A total of 147 eyes (83 patients) were evaluated. Mean postoperative UDVA and CDVA were 0.05 ± 0.11 and 0.02 ± 0.08 logMAR at 1 year and 0.13 ± 0.18 and 0.02 ± 0.09 logMAR at 5 years, respectively. More than 95% of eyes achieved CDVA of 20/25 or better at both follow-up periods. CDVA was unchanged or improved from one to three or more lines in all eyes. Preoperatively, mean spherical equivalent (SE) was -9.20 ± 3.02 diopters (D). At 1 year, the mean SE was -0.17 ± 0.26 D, with 91.53% of eyes within ±0.50 D and 100% of eyes within ±1.00 D of the target. At 5 years, the mean SE was -0.44 ± 0.47 D, with 67.4% of eyes within ±0.50 D and 90.1% of eyes within ±1.00 D of the target. Mean IOP was 12.74 ± 1.65 and 13.0 ± 2.03 mm Hg, at 1 and 5 years, respectively. No significant rise in IOP (> 20 mm Hg) occurred during the follow-up period. Mean ECD was 2,696 ± 358 and 2,645 ± 359 cells/mm
at 1 and 5 years, respectively, representing a non-significant loss of 0.43% from preoperative values (P = .304). Mean vault changed significantly from 398 ± 187 µm at 1 year to 340 ± 163 µm at 5 years (P < .001). No intraoperative or postoperative complications or adverse events occurred during the follow-up period.
The good long-term outcomes found in this study support the use of this lens with a central port design for the correction of moderate to high myopia. J Refract Surg. 2019;35(3):169-176..
Exosomes have been related to various disorders, but their study in relation to ocular pathologies has been limited. In this article, we analyze exosomes produced by corneal stromal cells from ...healthy individuals and from patients with keratoconus. The proteomic study allowed for the identification of 14 new proteins with altered expression, related to molecules previously associated with the pathology. miRNA analysis detected 16 altered species, including miR-184, responsible for familial severe keratoconus. The prediction of its potential biological targets identified 1121 genes, including some related to this pathology. Exosomes produced by keratoconic cells induced a marked increase in the migration of stromal cells and corneal epithelium, while those produced by healthy cells had no effect on stromal cells. Both types of nanovesicles reduced the proliferation of stromal and corneal cells, but those produced by healthy cells had less effect. Exosomes produced by healthy cells had concentration-dependent effects on the transcription of genes encoding proteoglycans by keratoconus cells, with a relative normalization observed at concentrations of 240 µg/mL. These results show the alteration of stromal exosomes in keratoconus and suggest an influence on the development of the pathology, although the use of healthy exosomes could also have therapeutic potential.
Purpose. To assess the long-term outcomes of implanting intrastromal corneal ring segments (ICRS) in paracentral keratoconic eyes. Methods. 58 eyes with paracentral keratoconus with coincident ...refractive, keratometric, and comatic axes were evaluated. Uncorrected (UDVA) and corrected (CDVA) distance visual acuity and refractive errors were recorded before and at all follow-up visits. The postoperative follow-up was 5 years. Patients were divided into two groups: group I (30 years old or younger) and group II (more than 30 years old). Results. The mean UDVA (logMAR) rose from a preoperative 0.83 ± 0.31 to a five-year postoperative 0.42 ± 0.33 (P<0.0001). The mean CDVA varied from 0.16 ± 0.17 to 0.11 ± 0.18 (P=0.0003). Both the UDVA and CDVA were stable over the postoperative period in both groups (P>0.05). The spherical equivalent and the refractive cylinder declined steeply after ICRS implantation in both groups (P<0.001), and were stable over the postoperative period (P>0.05). The keratometric values were also stable over the postoperative follow-up. Conclusion. Ferrara-type ICRS implantation in keratoconus that meets the characteristics of the sample under study reduces the refractive error at the same time as it improves postoperative UDVA and CDVA six months after surgery and that these results remain stable over five years of follow-up.
To evaluate the efficacy, predictability, safety, and stability of a new-model posterior chamber Implantable Collamer Lens phakic intraocular lens (pIOL) (V4c Visian) to correct myopia.
Private ...practice, Oviedo, Spain.
Case series.
This study enrolled patients who had implantation of a new pIOL design with a central hole for more natural aqueous flow, eliminating the need for neodymium:YAG iridotomy or peripheral iridectomy. The uncorrected (UDVA) and corrected (CDVA) distance visual acuities, refractive error, intraocular pressure (IOP), endothelial cell count, central vault, and adverse events were evaluated 6 months postoperatively.
The study enrolled 138 eyes (70 patients). The mean spherical equivalent decreased from -8.73 diopters (D) ± 2.54 (SD) preoperatively to -0.03 ± 0.19 D 6 months postoperatively; 98.5% of eyes were within ±0.50 D and 100% of eyes were within ±1.00 D. The mean UDVA and CDVA were 20/20 or better in 92.1% and 95.0% of eyes, respectively, at 6 months. The safety and efficacy indices were 1.01 and 1.00, respectively. Postoperatively, the IOP remained stable over time. No significant rises in IOP (including pupillary block) and no secondary cataract were found. After 6 months, the mean vault was 482.7 ± 210.5 μm (range 90 to 970 μm) and the mean endothelial cell loss was 8.5%.
Implantation of the pIOL was effective, predictable, safe, and stable for the correction of moderate to high myopic errors. This design, which avoids iridotomy or iridectomy, provided good IOP outcomes.
No author has a financial or proprietary interest in any material or method mentioned.
PDF
