Fernández-Vega Ophthalmological Institute

The combination of hearing loss and visual impairment in a single patient strongly suggests a genetic aetiology. However, after conventional testing, a considerable proportion of deafblindness cases remain without a genetic diagnosis. The aim of this study was to address this diagnostic gap. We developed an enhanced exome strategy that uses a whole-exome backbone complemented by spike-in capture probes for (i) low-coverage coding segments and clinically validated, non-coding regions (including deep intronic splice-altering sites and untranslated exonic sequences) across 659 genes associated with hearing loss and/or visual impairment, and (ii) mitochondrial DNA. With 66.6 million paired-end reads per sample, this methodology achieved coverage of at least 20 reads per base at 99.3% of target coding and non-coding positions of genes associated with deafness and/or blindness, as well as 98.8% of the whole exome. The enhanced exome approach correctly identified the genetic variants causative of deafness and/or blindness in 10 out of 10 cases with a previously known genetic cause, in 3 out of 10 additional cases that remained undiagnosed after extensive panel sequencing, and in 4 out of 4 cases that had not been genetically studied before. Comparison of the performance of two commercial bioinformatics platforms for enhanced exome interpretation revealed that eVAI consistently prioritised causative variants higher than, or as high as, VarSome Clinical, resulting in a tendency toward shorter interpretation times using the former. Both platforms offered the same diagnostic yield and both failed to correctly call one of the causative variants. In an era where many centres operate exome analysis through virtual panels, enhanced exome sequencing leverages the advantages of whole-exome and custom panel sequencing: it provides panel-like sensitivity for clinically actionable loci, while offering the flexibility to periodically reanalyse data and discover candidate genes.

BackgroundMulticomponent strategies can reduce benzodiazepine (BZD) use. BenzoStopJuntos (Spanish for “Stop Benzos Together”), a multidisciplinary deprescribing programme of the Andalusian Health Service, supports patients to taper/stop BZD through education, behavioral support, and non-pharmacological alternatives. We evaluated whether early changes (6 months) in risk perception and attitudes—and secondarily, quality of life—were associated with long-term discontinuation of BZD.MethodsIn a quasi-experimental pre–post study in two primary care centres (Seville, Spain; n = 243), the intervention included patient education, tapering support, and alternatives for anxiety/insomnia delivered by a multidisciplinary team. Primary outcomes were (a) short-term (6-month) changes in risk perception and attitudes and (b) long-term BZD discontinuation over 5.5 years; the secondary outcome was quality of life (WONCA/COOP), monitored to detect potential harms. Multivariable logistic regression examined whether 6-month changes in beliefs/attitudes predicted subsequent discontinuation, adjusting for sociodemographic and clinical factors.ResultsBZD discontinuation increased from 31.3 % at 6 months to 40.7 % at 5.5 years. Participants who considered BZD safe long-term were more likely to continue use (OR = 2.0; 95 % CI: 1.6–2.6). Fears of worsened anxiety/sleep strongly predicted persistence (OR = 4.7; 95 % CI: 3.6–6.1). Prior intermittent vs continuous use favored discontinuation (OR = 4.9; 95 % CI: 3.7–6.5). Quality of life improved in emotional, social, and physical domains, with no deterioration observed during follow-up.ConclusionsTailored education and behavioral strategies changed risk perceptions and attitudes, which in turn facilitated sustained BZD discontinuation without adverse effects on quality of life. Addressing patient beliefs and encouraging intermittent use patterns may enhance deprescribing success.Trial registrationClinicalTrials.govNCT06209827

BackgroundIsotretinoin is a vitamin A derivative used as a first-line treatment for moderate to severe acne. One of its most frequent side effects is dry eye disease (DED), in which tear film instability and neurosensory abnormalities play an etiologic role. The purpose of this research was to analyze changes in corneal innervation and its association with tear film integrity in patients treated with oral isotretinoin.MethodsTwenty-eight patients treated with oral isotretinoin and the same number of age and sex distribution-matched healthy volunteers were included in this observational case‒control study. They were examined by in vivo corneal confocal microscopy (IVCM) to quantify the corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), and corneal nerve fractal dimension (CNFrD) in addition to the presence of dendritiform cells, microneuromas, and visibility of axonal beadings. Tear film analysis was also performed, as was the perception of discomfort related to ocular surface disease.ResultsThe results of the comparative analysis of the isotretinoin group vs. the control group (mean [standard error]) were as follows: CNFD 18.57 [1.67] vs. 24. 57 [1.55] fibers per mm2 (p = 0.01); CNBD 19.05 [2.43] vs. 30.62 [3.53] branches per mm2 (p = 0.02); CNFL 13.90 [1.01] vs. 14.64 [0.66] mm per mm2 (p = 0.54); CNFrD 1.46 [0.005] vs. 1.49 [0.006] (p = 0.01); Schirmer test 5.7 [1.1] vs. 10.3 [0.5] millimeters (p < 0.001). The break-up time (BUT) was 5.70 [0.6] vs. 11.2 [0.2] seconds (p < 0.001). A linear regression equation model was developed for BUT (R2 = 0.48; 1-β = 0.98; p = 0.01) and CNFrD (R2 = 0.58; 1-β = 0.99; p = 0.002).ConclusionOral isotretinoin treatment promotes a vicious cycle of ocular surface disease that leads to damage to the subbasal nerve plexus. This damage increases with treatment time and impacts basal tear production.

Background/Objectives: To describe the pseudochamber-protected keratoplasty (PPK) procedure with the new Endo-K Pro® implant technique and report the clinical outcomes in patients at high risk for penetrating keratoplasty (PKP). Methods: This case series study included patients who required a PKP and had a high risk for corneal transplant failure. All cases underwent the PPK procedure with simultaneous Endo-K Pro® implantation and had a minimum follow-up of 12 months. Graft survival was the primary outcome (defined as a clear graft with an endothelial cell density >500 cells/mm2). Central corneal thickness (CCT), corrected distance visual acuity (CDVA), intraocular pressure (IOP), and complication rate were the secondary outcomes. Results: Twenty-five eyes (twenty-five patients) were included. The mean follow-up was 23.64 ± 8.2 months (range: 12-36 months). Graft survival was achieved in 23 of the 25 cases (92%). One eye had to be re-transplanted due to persistent oedema secondary to uncontrolled IOP. In two cases (8%), the graft failed three months after surgery when an anterior pseudochamber collapsed due to direct contact of donor endothelium and host tissue. Six eyes experienced host tissue protrusion that was successfully managed using an Nd: YAG laser (two eyes) or injecting a cohesive viscoelastic into the pseudochamber (four eyes). CDVA increased significantly during the follow-up period. No significant changes were found in IOP. No intra- or postoperative complications were reported. Conclusions: PPK with the Endo-K Pro® implant seems to be an effective and safe surgical approach as an alternative in high-risk patients for PKP, allowing full-thickness corneal transplantation without performing an open-sky procedure.

Purpose of ReviewThe aim of this review, is to present an updated revision of topical management of SAC and PAC, based on the available scientific evidence and focused on the impact of ophthalmic solution formulations on eye surface.Recent FindingsPhysicians treating ocular allergy should be aware of tear film and tear film disruption in SAC and PAC, and how eye drop composition and additives affect the physiology of the allergic eye.SummarySeasonal and perennial allergic conjunctivitis (SAC and PAC) are the most frequent causes of ocular allergy (OA), and both conditions are underdiagnosed and undertreated. SAC and PAC are immunoglobulin E (IgE)-mediated hypersensitivity reactions. The additional tear film disruption caused by the release of inflammatory mediators increases and exacerbates the impact of signs and symptoms and may trigger damage of the ocular surface. Comorbidities are frequent, and dry eye disease in particular must be considered. Clinical guidelines for the management of SAC and PAC recommend topical therapy with antihistamines, mast cells stabilizers or dualaction agents as first-line treatment, but care should be taken, as many medications contain other compounds that may contribute to ocular surface damage.

The included patients underwent two cycles of a 3-month PRGF treatment. At 6 months, symptomatology was evaluated using the OSDI and SANDE questionnaires, and ocular surface parameters were analyzed. The OSDI and SANDE values for frequency and severity demonstrated statistically significant improvements (p < 0.05). Ocular redness, corneal damage (corneal staining), and tear volume (Schirmer test) also exhibited statistically significant improvements (p < 0.05). No significant changes were observed in visual acuity or in the grade of meibomian gland loss. The use of PRGF in patients with congenital aniridia and ocular dryness symptoms led to significant improvements in symptomatology, ocular redness, and ocular damage. No adverse effects were observed during the use of PRGF.

To assess the clinical and aberrometric outcomes of a new Implantable Collamer Lens (EVO Viva ICL; STAAR Surgical) to correct moderate to high myopia and presbyopia. The study included 80 eyes of 40 patients who had bilateral EVO Viva ICL implantation. Uncorrected (UDVA) and corrected (CDVA) distance visual acuities, refraction, presbyopic add power, binocular through-focus visual acuity, total ocular spherical aberration (SA), coma aberration, and root mean square of ocular higher order aberrations (RMS HOAs) (i-Trace Aberrometer; Tracey Technologies) for a 4.5-mm pupil size were evaluated. The mean binocular postoperative UDVA and CDVA were 0.09 ± 0.19 and 0.02 ± 0.03 logMAR, respectively. The postoperative spherical equivalent was -0.61 ± 0.54 diopters (D). The presbyopic add power reduced from +1.31 ± 0.74 D preoperatively to +0.44 ± 0.58 D after surgery (P < .0001). The mean visual acuity was 0.1 logMAR or better (20/25 or better) across the vergence range from +0.50 to -1.50 D, better than 0.2 logMAR (20/32 or better) up to the vergence of -2.00 D, and remained better than 0.3 logMAR (20/40 or better) up to the vergence of -2.50 D. The total ocular aberrations induced by EVO Viva ICL were -0.34 ± 0.09 µm of SA, 0.24 ± 0.18 µm of coma, and 0.26 ± 0.12 µm of RMS HOAs. The outcomes support that the new ICL might be a good alternative for myopia and presbyopia correction in patients aged between 45 and 55 years. Further studies are needed to evaluate the threshold lens misalignment from which the patient´s visual quality would be affected. [J Refract Surg. 2023;39(9):589-596.].

The mechanism that could increase intraocular pressure (IOP) during scleral lens (SL) wear is not fully understood, although it may be related to compression of the landing zone on structures involved in aqueous humor drainage. Thirty healthy subjects were fitted with two SLs of different sizes (L1 = 15.8 mm, L2 = 16.8 mm) for 2 h in the right eye and left eye as a control. Central corneal thickness (CCT), parameters of iridocorneal angle (ICA), Schlemm's canal (SC), and optic nerve head were measured before and after wearing both SLs. IOP was measured with a Perkins applanation tonometer before and after lens removal and with a transpalpebral tonometer before, during (0 h, 1 h, and 2 h), and after lens wear. CCT increased after wearing L1 (8.10 ± 4.21 µm; p < 0.01) and L2 (9.17 ± 4.41 µm; p < 0.01). After L1 removal, the ICA parameters decreased significantly (p < 0.05). With L2 removal, nasal and temporal SC area and length were reduced (p < 0.05). An increased IOP with transpalpebral tonometry was observed at 2 h of wearing L1 (2.55 ± 2.04 mmHg; p < 0.01) and L2 (2.53 ± 2.22 mmHg; p < 0.01), as well as an increased IOP with Perkins applanation tonometry after wearing L1 (0.43 ± 1.07 mmHg; p = 0.02). In the short term, SL resulted in a slight increase in IOP in addition to small changes in ICA and SC parameters, although it did not seem to be clinically relevant in healthy subjects.

In-stent restenosis (ISR) is a major challenge in interventional cardiology. Both ISR and excessive skin healing are aberrant hyperplasic responses, which may be functionally related. However, the cellular component underlying ISR remains unclear, especially regarding vascular homeostasis. Recent evidence suggest that novel immune cell populations may be involved in vascular repair and damage, but their role in ISR has not been explored. The aims of this study is to analyze (i) the association between ISR and skin healing outcomes, and (ii) the alterations in vascular homeostasis mediators in ISR in univariate and integrative analyses. 30 patients with ≥1 previous stent implantation with restenosis and 30 patients with ≥1 stent without restenosis both confirmed in a second angiogram were recruited. Cellular mediators were quantified in peripheral blood by flow cytometry. Skin healing outcomes were analyzed after two consecutive biopsies. Hypertrophic skin healing was more frequent in ISR patients (36.7%) compared to those ISR-free (16.7%). Patients with ISR were more likely to develop hypertrophic skin healing patterns (OR 4.334 [95% CI 1.044-18.073], p=0.033), even after correcting for confounders. ISR was associated with decreased circulating angiogenic T-cells (p=0.005) and endothelial progenitor cells (p<0.001), whereas CD4+CD28null and detached endothelial cells counts were higher (p<0.0001 and p=0.006, respectively) compared to their ISR-free counterparts. No differences in the frequency of monocyte subsets were found, although Angiotensin-Converting Enzyme expression was increased (non-classical: p<0.001; and intermediate: p<0.0001) in ISR. Despite no differences were noted in Low-Density Granulocytes, a relative increase in the CD16- compartment was observed in ISR (p=0.004). An unsupervised cluster analysis revealed the presence of three profiles with different clinical severity, unrelated to stent types or traditional risk factors. ISR is linked to excessive skin healing and profound alterations in cellular populations related to vascular repair and endothelial damage. Distinct cellular profiles can be distinguished within ISR, suggesting that different alterations may uncover different ISR clinical phenotypes.

The purpose of this study is to evaluate the utility and safety of plasma rich in growth factors immunosafe eye drops (is-ePRGF) in the postoperative treatment of non-penetrating deep sclerectomy (NPDS). This is a case-control study in patients with open-angle glaucoma. Group one (control) was not treated with is-ePRGF, while group two (is-ePRGF) was treated (four times a day for four months). Postoperative evaluations were performed at one day, one month, three months and six months. The main outcomes were: intraocular pressure (IOP), microcysts in blebs with AS-OCT and the number of hypotensive eye drops. Preoperatively, group one (n = 48 eyes) and group two (n = 47 eyes) were similar in age (71.5 ± 10.7 vs. 70.9 ± 10.0 years; p = 0.68), IOP (20.6 ± 10.2 vs. 23.0 ± 9.0 mmHg; p = 0.26) and number of hypotensive drugs (2.7 ± 0.8 vs. 2.8 ± 0.9; p = 0.40). The IOP at six months dropped to 15.0 ± 8.0 mmHg (IOP reduction: -27.2%) and 10.9 ± 4.3 mmHg (IOP reduction: -52.6%) for group one and group two, respectively (p < 0.01). At six months, blebs with microcysts were 62.5% (group one) and 76.7% (group two). Postoperative complications were observed in 12 eyes (25%) for group one and in 5 eyes (11%) for group two (p = 0.06). No specific complications related to the use of is-ePRGF were identified. Topical is-ePRGF seems to reduce IOP and the rate of complications in the medium term after NPDS, so it can be considered as a possible safe adjuvant to achieve surgical success.