Keratoconus Diagnostic and Treatment Algorithms Based on Machine-Learning Methods.

The accurate diagnosis of keratoconus, especially in its early stages of development, allows one to utilise timely and proper treatment strategies for slowing the progression of the disease and provide visual rehabilitation. Various keratometry indices and classifications for quantifying the severity of keratoconus have been developed. Today, many of them involve the use of the latest methods of computer processing and data analysis. The main purpose of this work was to develop a machine-learning-based algorithm to precisely determine the stage of keratoconus, allowing optimal management of patients with this disease. A multicentre retrospective study was carried out to obtain a database of patients with keratoconus and to use machine-learning techniques such as principal component analysis and clustering. The created program allows for us to distinguish between a normal state; preclinical keratoconus; and stages 1, 2, 3 and 4 of the disease, with an accuracy in terms of the AUC of 0.95 to 1.00 based on keratotopographer readings, relative to the adapted Amsler-Krumeich algorithm. The predicted stage and additional diagnostic criteria were then used to create a standardised keratoconus management algorithm. We also developed a web-based interface for the algorithm, providing us the opportunity to use the software in a clinical environment.

Morphometric analysis of the lens in human aniridia and mouse Small eye.

Congenital aniridia is caused by heterozygous mutations in the PAX6 gene. In this disease, congenital iris and foveal hypoplasia is associated with juvenile onset cataract, glaucoma, and corneal keratopathy. In rodents, Pax6 mutations result in a congenital reduction in ocular size that is not typically described in human aniridia. Here, the ocular morphometry of aniridia patients is compared with the lens phenotype of Pax6+/tm1/Pgr mice to reveal whether there are species differences in Pax6 regulation of lens development and homeostasis. Ultrasound biometry (UBM) revealed that eleven percent of aniridia patients exhibited mild microphthalmia while the anterior chamber depth of aniridic eyes was significantly reduced from 6 months of age onward. Although aniridic lens thickness was normal from birth, it was significantly decreased in aniridic lenses older than 30. Notably, 86% of aniridic lenses exhibited cataractous changes in this cohort. In addition, a significant proportion of aniridia patients develop lens subluxation as they age associated with reduced lens diameter as measured by anterior segment optical coherence tomography (AS-OCT). Analysis of young adult Pax6+/tm1/Pgr mouse lenses by micro-computed tomography (microCT), bright field and dark field imaging revealed that they are reduced in size but did not exhibit overt cataracts at this age. Overall, this study reveals that congenital microphthalmia as assessed by axial length, or microphakia, as assessed by lens thickness, are not typical in human aniridia, although these are primary manifestations of Pax6 mutations in mice, suggesting that PAX6 regulates some aspects of lens development differently between these species.

Expanding the phenotype of CRYAA nucleotide variants to a complex presentation of anterior segment dysgenesis.

BACKGROUND: Mutations in CRYAA, which encodes the α-crystallin protein, are associated with a spectrum of congenital cataract-microcornea syndromes. RESULTS: In this study, we performed clinical examination and subsequent genetic analysis in two unrelated sporadic cases of different geographical origins presenting with a complex phenotype of ocular malformation. Both cases manifested bilateral microphthalmia and severe anterior segment dysgenesis, primarily characterized by congenital aphakia, microcornea, and iris hypoplasia/aniridia. NGS-based analysis revealed two novel single nucleotide variants occurring de novo and affecting the translation termination codon of the CRYAA gene, c.520T > C and c.521A > C. Both variants are predicted to elongate the C-terminal protein domain by one-third of the original length. CONCLUSIONS: Our report not only expands the mutational spectrum of CRYAA but also identifies the genetic cause of the unusual ocular phenotype described in this report.

One week of levofloxacin plus dexamethasone eye drops for cataract surgery: an innovative and rational therapeutic strategy.

BACKGROUND: Cataract surgery is the most common operation performed worldwide. A fixed topical corticosteroid-antibiotic combination is usually prescribed in clinical practice for 2 or more weeks to treat post surgical inflammation and prevent infection. However, this protracted schedule may increase the incidence of corticosteroid-related adverse events and notably promote antibiotic resistance. METHODS: This International, multicentre, randomized, blinded-assessor, parallel-group clinical study evaluated the non-inferiority of 1-week levofloxacin/dexamethasone eye drops, followed by 1-week dexamethasone alone, vs. 2-week gold-standard tobramycin/dexamethasone (one drop QID for all schedules) to prevent and treat ocular inflammation and prevent infection after uncomplicated cataract surgery. Non-inferiority was defined as the lower limit of the 95% confidence interval (CI) around a treatment difference >-10%. The study randomized 808 patients enrolled in 53 centres (Italy, Germany, Spain and Russia). The primary endpoint was the proportion of patients without anterior chamber inflammation on day 15 defined as the end of treatment. Endophthalmitis was the key secondary endpoint. This study is registered with EudraCT code: 2018-000286-36. RESULTS: After the end of treatment, 95.2% of the patients in the test arm vs. 94.9% of the control arm had no signs of inflammation in the anterior chamber (difference between proportions of patients = 0.028; 95% CI: -0.0275/0.0331). No case of endophthalmitis was reported. No statistically significant difference was evident in any of the other secondary endpoints. Both treatments were well tolerated. CONCLUSIONS: Non-inferiority of the new short pharmacological strategy was proven. One week of levofloxacin/dexamethasone prevents infection, ensures complete control of inflammation in almost all patients and may contain antibiotic resistance.

Correction: One week of levofloxacin plus dexamethasone eye drops for cataract surgery: an innovative and rational therapeutic strategy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Clinical and morphological manifestations of aniridia-associated keratopathy on anterior segment optical coherence tomography and in vivo confocal microscopy.

PURPOSE: The study aimed to evaluate clinical and morphological changes in the limbal palisades of Vogt (POV) at different stages of aniridia-associated keratopathy (AAK) and to assess possible utility of anterior segment optical coherence tomography (AS-OCT) for the visualization of limbal progenitor structures as it correlates to laser scanning confocal microscopy (LSCM) data. METHODS: The study involved 32 patients (59 eyes) with congenital aniridia. AAK stage was defined based on biomicroscopy. Assessment of limbal zone and detection of POVs in identical areas was performed by LSCM (HRT3) and AS-OCT (RTVue XR Avanti) using 3D Cornea (En Face mode) and Cornea Cross Line protocols. RESULTS: Intact and changed POVs were found in 8/8 stage 0 eyes, in 1/21 stage I and 2/13 stage II eyes. Spearman's correlation coefficient in assessing the consistency of the POV diagnostic results by LSCM and AS-OCT for the inferior limbus was rS = 0.85 (P < 0.05), for the superior limbus - rS = 0.53 (P < 0.05). AS-OCT was less sensitive for detection of partially present POVs in superior limbus. The negative correlation between AAK stage and POV preservation was determined (rS = -0.5, P < 0.05). There was no correlation between AAK stage and patient age (rS = 0.235, P = 0.209). Three patients with PAX6 3' deletion showed stage 0 AAK with intact or slightly disturbed POVs morphology and transparent cornea. CONCLUSION: AS-OCT may be an additional diagnostic tool for POV visualization in vivo in aniridic patients. Its diagnostic accuracy is subject to selection of anatomic region, nystagmus and the degree of POV degradation.

Initial results of trifocal diffractive IOL implantation.

BACKGROUND: Bifocal intraocular lenses (IOL) are designed to reduce dependence on eyeglasses after surgery, but they cannot provide full range of vision, and have a drop of visual acuity in the intermediate distance. This problem may be solved with a trifocal lens, which produces three useful focal points. This study was conducted to evaluate clinical outcomes, functional vision and spectacle independence in patients with trifocal diffractive IOLs. METHODS: Thirty-six eyes after implantation of diffractive intraocular lens MIOL-Record were evaluated. This IOL has a diffractive lens profile binary in phase and produces three useful foci. Outcome measures recorded 6 months postoperatively were uncorrected and distance-corrected (far, near, intermediate) visual acuities, contrast sensitivity (under photopic and mesopic condition), root-mean-square (RMS) of higher order aberrations (HOA), patients' quality of life (visual function questionnaire VFQ-25, halos and glare presence, overall satisfaction), and spectacle independence. RESULTS: Postoperatively, monocularly, the uncorrected (UDVA) and the corrected distance visual acuity (CDVA) were 0.74 +/- 0.21 and 0.86 +/- 0.23 respectively (P < 0.05). No differences were found between uncorrected (UNVA)-0.85 +/- 0.13 and best distance-corrected near visual acuity (CNVA) 0.89 +/- 0.12 (P > 0.05). The uncorrected (UIVA) and best distance-corrected acuities of intermediate vision (CIVA) at 50 cm were 0.58 +/- 0.16 and 0.6 +/- 0.2 respectively. The photopic contrast sensitivity was within the standard normal range. But under dim light conditions it was inferior at all spatial frequencies by more than 0.2 logarithmic units. The mean aberration values were: total HOA RMS-0.816 +/- 0.362 mum, spherical aberration (SA)-0.207 +/- 0.136 mum, coma-0.335 +/- 0.206 mum. The percentage of patients achieving spectacle freedom was 94%. On the questionnaire, 25% of patient noted nighttime halos; glare difficulty was reported by 16.7% of patients, difficulties with night vision persisted in 22.3% of cases. CONCLUSION: Diffractive trifocal intraocular lens MIOL-Record provided good uncorrected distance, intermediate and near vision, gave high rates of spectacle freedom and overall patient satisfaction.

Artificial iris-lens diaphragm in reconstructive surgery for aniridia and aphakia.

PURPOSE: To determine the efficacy and safety of surgical implantation of artificial iris-lens diaphragm in patients with anatomic or functional iris deficiencies, aphakia or cataract. SETTING: Svyatoslav Fyodorov MNTK Eye Microsurgery, Cheboksary, Russia. METHODS: Twenty eyes of 19 consecutive patients with combined iris and lens pathology of traumatic or congenital etiology were identified for an interventional noncomparative case series. The newly proposed model of an elastic iris-lens diaphragm with a colored haptic and additional support elements was implanted using various fixation approaches. RESULTS: Fifteen eyes (75%) experienced improvement in corrected visual acuities. The best spectacle-corrected visual acuity (BSCVA) in 2 eyes did not change, while the uncorrected visual acuity (UCVA) in these eyes increased. There were 3 eyes in which BSCVA deteriorated with no change or even slight improvement in UCVA. All patients were satisfied with the cosmetic results of the surgery and reported a decrease in glare and photophobia. There was 1 intraoperative complication of vitreous hemorrhage. Postoperatively, 2 cases of hyphema, 1 case of ciliochoroidal detachment, 4 eyes with exaggerated immediate postoperative reaction, and 1 eye with persistent low-grade cyclitis were observed. In 1 eye, there was persistent intraocular pressure rise. One eye showed signs of cystoid macular edema. No iris-lens diaphragm decentrations and no new or extensions of old retinal detachments were seen during the follow-up period. CONCLUSIONS: Artificial iris-lens diaphragm implantation effectively improved postoperative outcomes by correcting aphakia, reducing glare disability, and addressing cosmetic issues faced by iris-deficient, and aphakic or cataract patients. Although the iris-lens diaphragm appears to be safe, long-term results must be clarified in studies with longer follow-up and a larger patient population.