Outcomes of two different treatment modalities in mild to moderate keratoconus.

PURPOSE: To describe visual and refractive outcomes of intrastromal corneal ring segments (ICRS) and toric implantable collamer lenses (TICL) implantation in cases of mild and moderate keratoconus. METHODS: A prospective descriptive interventional case series. 40 eyes were allocated into two groups. First group (20 eyes) was treated with corneal collagen crosslinking (CXL) 1 month after ICRS implantation and the second group was treated using TICL after 1 year of CXL. RESULTS: Both groups showed statistically significant improvement in spherical equivalent, cylindrical refraction, uncorrected visual acuity (UCVA) and best corrected visual acuity (BCVA) over the follow-up period. CONCLUSION: Both ICRS and TICL are effective in treatment of mid and moderate keratoconus with more predictable visual results with TICL.

Epidemiology, clinical profile and treatment outcomes of bacterial and fungal keratitis.

PURPOSE: The purpose of the study is to determine the microbiological etiology, epidemiological factors, and clinical profile and treatment outcomes of infective keratitis in Ophthalmology department, Minia University, Egypt. METHODS: Prospective, nonrandomized, observational clinical series of cases, including 150 patients with mean age 30 (range 12 to 85 years), 90 patients (60%) were males and 60 (40%) were females, clinically diagnosed as infective corneal ulcer, attending the Ophthalmology Department-Faculty of Medicine. Minia University, Minia, Egypt. From December 2018 to December 2020. Detailed history taking and all clinical findings were collected. Corneal scrapings were obtained from patients and subjected to staining and culture for bacterial and fungal pathogens; Bacterial and fungal growth were identified by standard laboratory procedures. RESULTS: Corneal trauma by a vegetative matter was the commonest risk factor associated with infective keratitis in 92 cases (61.3%). Smear and culture was positive in 83 cases (58.4%) of 142 corneal scrapings obtained, of which 60 cases were fungal (72.3%), 21 cases were bacterial (25.3%) and two cases were mixed bacterial and fungal (2.4%), Aspergillus species was the commonest fungal species isolated in fungal keratitis. One hundred forty-two cases (94.67%) healed completely with scar. Only six cases (4%) required evisceration due to aggressive presentation from the start and keratoplasty was performed for two cases (1.33%). CONCLUSIONS: Fungal keratitis was the commonest type in cases attending to our department. Adequate diagnosis, management and follow-up helped in achieving high successful curative outcomes. CLINICAL TRIAL NUMBER: Clinical Trials.gov ID: NCT04894630. Time of registration 1 December 2018.

Association of VEGF Gene Family Variants with Central Macular Thickness and Visual Acuity after Aflibercept Short-Term Treatment in Diabetic Patients: A Pilot Study.

INTRODUCTION: Diabetic retinopathy (DR) is one of the major vision-threatening causes worldwide. Searching for an individualized therapeutic strategy to prevent its progress is challenging. OBJECTIVE: This work aimed to investigate the association of angiogenesis-inducer vascular endothelial growth factor (VEGF) gene family and related receptor variants (rs833069, rs12366035, rs7664413, rs7993418, and rs2305948) with susceptibility of DR and the response to 1 dose of aflibercept treatment in type 2 diabetes mellitus (T2DM). METHODS: Consecutive eligible patients with T2DM (n = 125) and 110 unrelated controls were enrolled in this preliminary prospective case-controlled study. Genotyping was identified using TaqMan real-time PCR. Adjusted odds ratio (OR) with 95% confidence interval (CI) was applied to assess the strength of the association with the clinical/ophthalmological characteristics and early response to intravitreal aflibercept treatment in terms of improved visual acuity (BCVA) and central macular thickness (CMT). RESULTS: We found that both VEGFB rs12366035 and VEGFC rs7664413 conferred higher risk for DR progression under allelic (OR [95% CI]: 1.71 [1.07-2.74]), homozygote comparison (3.55 [1.32-9.57]), and recessive (3.77 [1.43-9.93]) models for the former and under allelic (2.09 [1.25-3.490, homozygote comparison (2.76 [1.02-7.45]), and recessive (2.62 [0.98-6.98] models for the latter. In contrast, VEGFR1 rs7993418 conferred protection against DR under heterozygote comparison and dominant models. The rs12366035*T/T genotype showed the worst pretreatment BCVA score (0.35 ± 0.24) compared to other corresponding genotypes (0.66 ± 0.26 in C/T and 0.54 ± 0.25 in C/C carriers) (p = 0.008). Meanwhile, patients with rs7993418*G/G of VEGFR1 exhibited a significant reduction in CMT after aflibercept injection (12.26 ± 35.43 µ in G/G vs. 3.57 ± 8.74 µ in A/A) (p = 0.037). CONCLUSIONS: Polymorphisms of the studied VEGF/receptors could be considered as genetic risk factors of DM/DR development and could play an important role in aflibercept early response for DR patients in the study population.

Duloxetine protects against experimental diabetic retinopathy in mice through retinal GFAP downregulation and modulation of neurotrophic factors.

Diabetic retinopathy (DR) is recognized as one of the leading causes of blindness worldwide. Searching and validation for a novel therapeutic strategy to prevent its progress are promising. This work aimed to assess the retinal protective effects of duloxetine (DLX) in Alloxan-induced diabetic mice model. Animals were equally and randomly divided to four groups (eight mice per group); group 1: is the control group, 2: diabetic group, 3&4: diabetic and after 9 weeks received DLX for 4 weeks (15 mg/kg and 30 mg/kg), respectively. Quantitative real-time PCR (qPCR) analysis revealed nerve growth factor (NGF), inducible nitric oxide synthase (iNOS) and transforming growth factor beta (TGF-ß) genes upregulation in the diabetic group compared to controls. Also, increased retinal malondialdehyde (MDA) and the decline of reduced glutathione (GSH) levels were observed. The morphometric analysis of diabetic retina revealed a significant reduction in total retinal thickness compared to control. Diabetic retinal immunostaining and Western blot analyses displayed glial fibrillary acidic protein (GFAP) and vascular endothelial cell growth factor (VEGF) proteins expression upregulation as well as glucose transporter-1 (GLUT-1) downregulation comparing to controls. However, DLX-treated groups showed downregulated NGF, iNOS, and TGF-ß that was more obviously seen in the DLX-30 mg/kg group than DLX-15 mg/kg group. Furthermore, these groups showed amelioration of the oxidative markers; MDA and GSH, retaining the total retinal thickness nearly to control, GFAP and VEGF downregulation, and GLUT-1 upregulation compared to diabetic group. Taken together, it could be summarized that duloxetine can attenuate DR via the anti-inflammatory and the anti-oxidative properties as well as modulating the angiogenic and the neurotrophic factors expressions. This could hopefully pave the road to be included in the novel list of the therapeutic regimen for DR after validation in the clinic.

Deciphering the role of circulating lncRNAs: RNCR2, NEAT2, CDKN2B-AS1, and PVT1 and the possible prediction of anti-VEGF treatment outcomes in diabetic retinopathy patients.

PURPOSE: Putative roles of long non-coding RNAs (lncRNAs) as indicators for diabetic retinopathy (DR) and associated complications are beginning to emerge. We aimed to evaluate a panel of circulating hyperglycemia-related lncRNAs: RNCR2, NEAT2, CDKN2B-AS1, and PVT1 in type 2 diabetes patients with/without DR and to correlate their levels with the clinical characteristics and response to aflibercept intravitreal injection in terms of visual acuity (VA) improvement, central macular thickness (CMT) decline, and macular edema resolution after 4 weeks of the initial injection. METHODS: Pre-treatment plasma relative expression levels of the specified lncRNAs were quantified in 130 consecutive patients with diabetes (75 and 55 with/without DR, respectively) and 108 controls using quantitative real-time PCR. RESULTS: One month after aflibercept injection, significant reductions in CMT and VA were observed in DR cohorts. The four lncRNAs were over-expressed in DM compared with those in controls. However, downregulated baseline plasma levels of RNCR2 and NEAT2 were observed in glycemic-controlled DR patients. None of the lncRNAs showed a correlation with the severity of retinopathy or drug response. CONCLUSION: Though circulating levels of the analyzed lncRNAs did not show an association with DR progression or aflibercept therapy response, the expression pattern demonstrated good diagnostic performance in differentiating DM from controls and DR.

Topical Eugenol Successfully Treats Experimental Candida albicans-Induced Keratitis.

PURPOSE: To determine the efficacy of eugenol for the treatment of Candida keratitis in an experimental model. METHODS: The in vitro antifungal activity of eugenol and fluconazole was tested against C. albicans strains via the microbroth dilution method. An experimental model of Candida albicans keratitis was used. Rabbits were classified into those that received no treatment (control; group 1) and those that started eugenol treatment immediately (group 2) or after 4 days (group 3) of keratitis induction (n = 12-16 rabbits/group). The 2 treatment groups were assigned to 50 µL of 4 mg/mL eugenol drops hourly for 15 days, while the control group received saline. Corneal penetration of eugenol was measured using HPLC, and corneal toxicity was evaluated clinically and histopathologically. RESULTS: The in vitro minimum inhibitory concentrations of eugenol and fluconazole against C. albicans were 2 and > 0.4 mg/mL, respectively. A 4-mg/mL preparation of eugenol in propylene glycol was the maximum nontoxic dose on rabbit corneas as suggested by clinical and histopathologic findings. At least 75% of all eugenol-treated eyes recovered from keratitis, with improvement in the remaining 25% of the eyes compared to controls. CONCLUSIONS: Eugenol can act as a natural, safe, and effective treatment for fungal keratitis, regardless of whether treatment is started immediately or after 4 days of keratitis induction.

Enhancements after cataract surgery.

PURPOSE OF REVIEW: To provide a review of the recent literature on the indications and results of refractive and nonrefractive enhancements after cataract surgery. RECENT FINDINGS: Laser in-situ keratomileusis proves to be the most accurate procedure to correct residual refractive error after cataract surgery. Other lens-based procedures can be used for the enhancement after cataract surgery but with lower predictability. Depending on the cause of the visual problem, these may be toric intraocular lens (IOL) rotation for excess residual cylinder and IOL exchange for unsatisfied patients with multifocal IOL or for IOL dislocation. SUMMARY: Modern lens removal techniques and advanced preoperative diagnostic methods allow most cataract patients to be spectacle-independent for distance and sometimes also for near. Refractive considerations are integrated into modern cataract surgery and these days, patients expect an adequately predicted refractive outcome. Despite such advances in cataract surgery, unsatisfactory refractive and visual outcomes occasionally occur and in these cases, the enhancement after cataract surgery is required to achieve the best final visual outcome.

Refractive surgery following corneal graft.

PURPOSE OF REVIEW: To review the different surgical procedures for management of postkeratoplasty refractive errors after total suture removal. RECENT FINDINGS: There are different surgical options to address residual refractive errors that frequently occur after corneal transplantation. The correction can be done on the corneal surface or intraocular with intraocular lens (IOL) implantation which requires complete tectonic and refractive stability after suture removal. The most commonly used procedures are photorefractive keratectomy, laser in-situ keratomileusis and Phakic IOLs. Keratoplasty has been profited by recent advances in refractive surgery. Custom excimer laser ablation is an alternative way to treat irregular errors. New IOL modalities are good practical options for a wide range of errors. Femtosecond laser, as a new option in the toolbox, can modify corneal grafting refractive results and assist corrective refractive procedures. SUMMARY: Although being the most successful organ transplantation, keratoplasty is usually followed by significant ametropia. Different corrective modalities exist and the choice should fit ocular conditions, patient requirements, surgeon skills and the available technologies. Recent advances in ophthalmic surgery have improved the outcomes.

Management of residual refractive error after cataract surgery.

PURPOSE OF REVIEW: To provide a review of the recent literature on the management of residual refractive error after cataract surgery. RECENT FINDINGS: Laser in-situ keratomileusis (LASIK) is the most accurate procedure to correct residual refractive error after cataract surgery. Lens-based procedures, such as intraocular lens (IOL) exchange or piggyback lens implantation, are also possible alternatives in cases with extreme ametropia, corneal abnormalities, or in situations where excimer laser is not available. In this review, we found that Piggyback IOL were safer and more accurate than IOL exchange. SUMMARY: Emmetropia is our main target today in modern cataract surgery. Accurate biometric analysis, selection and calculation of the adequate IOL, and modern techniques for cataract surgery all help surgeons to move toward the goal of cataract surgery as a refractive procedure free from refractive error. However, in spite of all these inputs, residual refractive error still occasionally occurs after cataract surgery and LASIK seems to be the most accurate method for its correction.

Role of Anterior Segment Optical Coherence Tomography in Staging and Evaluation of Treatment Response in Infectious Keratitis.

PURPOSE: The aim of this study was to evaluate the role of anterior segment optical coherence tomography during follow-up of infectious keratitis and to assess response to treatment. METHODS: This was a prospective, consecutive, observational clinical series of cases. Twenty-three eyes of 23 patients with clinically proven fungal keratitis were included in the study. The patients received medical treatment according to clinical diagnosis, and follow-up was performed weekly. Slit-lamp examination and photography, and anterior segment optical coherence tomography were performed at initial and follow-up visits until corneal healing occurred. The main outcome measures included infiltrate depth, width, and density; central corneal thickness; minimal corneal thickness; corneal thickness at the site of the lesion; and stromal thickness at the center of the lesion. RESULTS: Twenty-three eyes of 23 patients (17 men and 6 women), mean age 42.5 ± 19 (8-66) years, were clinically diagnosed with fungal keratitis. Localization was central in 14 cases and paracentral/peripheral in 9 cases. Healing time was 6 to 12 weeks. Minimal corneal thickness, corneal thickness at the site of lesion, and stromal thickness at the center of lesion, and also infiltrate width and depth changed significantly from the first visit to the healing stage at the last follow-up (0.009, 0.001, 0.007, 0.001, and <0.001, respectively). CONCLUSIONS: In cases of fungal keratitis, anterior segment optical coherence tomography can provide the clinician with a quantitative assessment of a number of corneal parameters that can be used to determine effectiveness of therapy and confirm complete healing of the lesions that cannot be achieved by clinical evaluation. CLINICAL TRIAL REGISTRATION: The study was registered in Clinical Trials.gov with NCT04969640.

Type 2 diabetes and thyroid cancer: Synergized risk with rising air pollution.

Diabetes is a complex condition, and the causes are still not fully understood. However, a growing body of evidence suggests that exposure to air pollution could be linked to an increased risk of diabetes. Specifically, exposure to certain pollutants, such as particulate Matter and Ozone, has been associated with higher rates of diabetes. At the same time, air pollution has also been linked to an increased risk of thyroid cancer. While there is less evidence linking air pollution to thyroid cancer than to diabetes, it is clear that air pollution could have severe implications for thyroid health. Air pollution could increase the risk of diabetes and thyroid cancer through several mechanisms. For example, air pollution could increase inflammation in the body, which is linked to an increased risk of diabetes and thyroid cancer. Air pollution could also increase oxidative stress, which is linked to an increased risk of diabetes and thyroid cancer. Additionally, air pollution could increase the risk of diabetes and thyroid cancer by affecting the endocrine system. This review explores the link between diabetes and air pollution on thyroid cancer. We will discuss the evidence for an association between air pollution exposure and diabetes and thyroid cancer, as well as the potential implications of air pollution for thyroid health. Given the connections between diabetes, air pollution, and thyroid cancer, it is essential to take preventive measures to reduce the risk of developing the condition.

Combined Platelet Rich Plasma and Amniotic membrane in the treatment of Perforated Corneal Ulcers.

PURPOSE: To report the outcomes of using synthetic amniotic membrane with platelet rich plasma for the primary management of corneal perforations. SETTING: Ophthalmology department. Faculty of Medicine, Minia University, Minia, Egypt. METHODS: A case series of 10 patients diagnosed with corneal perforation underwent emergency surgical procedure for repair of the perforation through the implantation of synthetic amniotic membrane with platelet-rich plasma clot under it and the application of platelet-rich plasma eye drops, with a follow up period of up to 4 weeks. RESULTS: All cases demonstrated formation of adequate intraocular pressure digitally, within the first 7 days, and all cases showed complete sealing of the corneal perforation within the 4 weeks follow up period, mild symptoms were reported only in the 1st postoperative week like foreign body sensation and lacrimation. 3 of the treated patients underwent penetrating keratoplasty after 6 months with satisfactory visual outcomes. CONCLUSION: The combination of amniotic membrane implant and platelet rich plasma in both the clot and eye drop forms is an effective and easy accessible method for the primary management of corneal perforations.

Astigmatic change as a predictor of intrastromal corneal ring segment late extrusion.

PURPOSE: To evaluate changes in keratoconic corneas implanted with intrastromal corneal ring segments (ICRSs) that have been explanted because of late extrusion of the segment after >2 years. SETTING: Vissum Miranza, Alicante, Spain; OftalmoSalud, Lima, Peru; Minya University Hospital, Egypt. DESIGN: Retrospective multicenter case series. METHODS: 23 keratoconic corneas that were implanted for ≥2 years and explanted because of natural extrusion of the segment. Clinical measures of visual, refractive, topographic, pachymetric, and aberrometric data were analyzed. To perform exploratory factor analysis, the Kaiser-Meyer-Olkin (KMO) test was used to evaluate sampling adequacy. Factor analysis with VARIMAX rotation was used to determine the main factors of the inventory. RESULTS: The mean time interval was 5 years. Topographic findings were reversed nearly to the baseline level after segment explantation (Km: 48.97 ± 3.47 D pre implantation and 47.60 ± 3.67 D after explantation, P =.374). Significant worsened in refractive cylinder was found pre-ICRS extrusion (‒2.54 ± 3.40 D after implantation and ‒3.96 ± 1.72 before extrusion, P < .05). The main factor obtained in the preimplantation moment included keratoconus grade, keratometric readings, and visual acuities. After ICRS implantation, the most strength components were the refractive cylinder, corrected distance visual acuity, and uncorrected distance visual acuity. Corneal aberrations were the main factors in the pre-explantation analysis. CONCLUSIONS: ICRSs were safely extracted, with a reversal of the corneal topographic data to the preoperative level. A significant astigmatic change was shown in patients implanted with ICRSs before late extrusion of the segment, suggesting the role of this parameter as a prognostic factor of extrusion.

Surgery for glaucoma in modern corneal graft procedures.

Glaucoma is a common cause of vision loss after corneal transplantion and is considered a major risk factor for graft failure. Glaucoma may be present before corneal transplant surgery, or increased intraocular pressure may develop after keratoplasty in up to one-third of patients. Pre-existing glaucoma should be controlled before keratoplasty, either medically or surgically. For postkeratoplasty increase in intraocular pressure; identifying the risk factors allows appropiate follow-up and management. Patients undergoing anterior lamellar keratoplasty may take advantage of reduced rates of postkeratoplasty glaucoma. Glaucoma also complicates eyes with endothelial keratoplasties, mostly related to management of intraocular pressure spikes derived from anterior chamber air bubbles. Nevertheless, the severity is less, and the intraocular pressure is more easily controlled when compared with penetrating keratoplasty. Adequate management of glaucoma that develops before or after keratoplasty may save eyes from irreversible damage to the optic nerve and increase graft survival.

Three-snip punctoplasty versus perforated plugs for management of lacrimal punctal stenosis.

PURPOSE: To compare rectangular three-snip punctoplasty and polyvinylpyrrolidone-coated perforated punctal plugs for treatment of acquired lacrimal punctal stenosis. PATIENTS AND METHODS: In a prospective comparative non-randomized interventional study, 80 eyes with acquired lacrimal punctal stenosis were classified into two groups. Group A was treated by insertion of polyvinylpyrrolidone-coated perforated punctal plugs (FCI ophthalmics)™ and Group B was treated by rectangular three-snip punctoplasty. The study was done in Minia University Hospital between January 2018 and April 2019. Exclusion criteria included allergic punctal stenosis, lid malposition, and lacrimal obstruction distal to the punctum. All patients were subjected to complete history taking, slit lamp examination of tear meniscus height, fluorescein dye disappearance test, punctal position, shape, size, grading of stenosis, and grading of epiphora. RESULTS: The mean age of the patients was 43.85 ± 14.93 years. They were 30 females and 10 males. Eepiphora Grade 3 or 4, improved postoperatively to Grade 0 or 1 in 97.5% of eyes in Group A versus 55% of eyes in Group B. All eyes (100%) in Group A versus 21 eyes (52.5%) in Group B improved regarding fluorescein dye disappearance test grade (p < 0.001). Restenosis did not occur after plug removal, while it occurred in 10% of eyes subjected to three-snip punctoplasty. CONCLUSION: Perforated punctal plugs and three-snip punctoplasty are safe and effective in treatment of punctal stenosis. However, perforated plugs are less invasive, better tolerated, and have more stable results compared to three-snip punctoplasty.

The Value of Anterior Segment Optical Coherence Tomography in Different Types of Corneal Infections: An Update.

Anterior segment optical coherence tomography (AS-OCT) is a modality that uses low-coherence interferometry to visualize and assess anterior segment ocular features, offering several advantages of being a sterile and noncontact modality that generates high-resolution cross-sectional images of the tissues. The qualitative and quantitative information provided by AS-OCT may be extremely useful for the clinician in the assessment of a wide spectrum of corneal infections, guiding in the management and follow-up of these patients. In clinical practice, infections are routinely evaluated with slit-lamp biomicroscopy, an examination and imaging modality that is limited by the physical characteristics of light. As a consequence, the depth of pathology and the eventually associated corneal edema cannot be accurately measured with the slit-lamp. Therefore, it represents a limit for the clinician, as in vivo information about corneal diseases and the response to treatment is limited. Resolution of corneal infection is characterized by an early reduction in corneal edema, followed by a later reduction in infiltration: both parameters can be routinely measured with standardized serial images by AS-OCT.

Evaluation of acquired punctal stenosis using anterior segment optical coherence tomography.

BACKGROUND/OBJECTIVES: The aim of this article was to study the lower punctum parameters in patients with acquired punctal stenosis using spectral-domain anterior segment optical coherence tomography. SUBJECTS/METHODS: This was a prospective nonrandomized study that included two groups. Group 1 was composed of 32 puncta from 32 subjects (11 males and 21 females, aged 40-62 years) with epiphora and clinically diagnosed punctal stenosis. Group 2 (control group) included 30 puncta from 30 normal subjects (10 males and 20 females, aged 43-63 years). Anterior segment optical coherence tomography was employed to evaluate lower punctum parameters in all subjects; the inner and outer punctal diameters as well as punctal depth were measured. RESULTS: External punctal diameter (mean: 466.1 ± 120.3 µm), internal punctal diameter (mean: 173.4 ± 55.6 µm) and punctal depth (mean: 188.4 ± 67 µm) values in Group 1 were statistically significantly lower than those in Group 2 (mean: 745.7 ± 156.9 µm, mean: 384 ± 119.1 µm, and mean: 284.9 ± 57.7 µm, respectively). CONCLUSION: Anterior segment optical coherence tomography could possibly be used as a noncontact and noninvasive diagnostic modality for evaluating and measuring the lower punctum in patients with punctal stenosis. Further research is required to develop a normative database and grading system for stenosed puncta and to correlate the degree of stenosis with the severity of epiphora.

Incidence and Reasons for Intrastromal Corneal Ring Segment Explantation.

PURPOSE: To determine the main causes of intrastromal corneal ring segment (ICRS) explantation and define the incidence rate. DESIGN: Multicenter, observational consecutive case series. METHODS: Consecutive cases of ICRSs explanted in the last 10 years were reviewed. Clinical data included age of the patients at explantation, reasons for implantation and explantation, date of implantation and explantation, tunnel creation technique, and ICRS type. Main outcomes measures were the reasons for ICRS removal and the incidence rate. RESULTS: During the study period, 121 ICRSs (119 patients) were explanted, with an explantation rate of 5.60%. Functional failure (74 eyes, 61.16%) represents the main cause for ICRS removal: of them, 48 (39.67%) ICRSs were removed for refractive failure and 26 (21.49%) in the setting of a keratoplasty related to poor visual performance of the implanted eye. In addition, 47 eyes (38.84%) had ICRS removal for anatomic failure: among them, 36 (29.75%) were explanted for spontaneous extrusion (overall extrusion rate: 1.58%), 7 (5.79%) for suspected infectious keratitis, 3 (2.48%) for corneal melting, and 1 (0.83%) for corneal perforation. Mild cases of keratoconus were more prone to be explanted because of a loss of the initial improved visual acuity, whereas spontaneous extrusion happened often in advanced cases of keratoconus. CONCLUSIONS: We report the largest series of ICRS explantation as of this writing. The main cause of explantation was functional refractive failure followed by spontaneous extrusion of the ICRS, that is, correlated to an anatomic failure at the site of implantation in an advanced disease.

Association of Collagen Gene (COL4A3) rs55703767 Variant With Response to Riboflavin/Ultraviolet A-Induced Collagen Cross-Linking in Female Patients With Keratoconus.

PURPOSE: To investigate for the first time the association of collagen COL4A3 (rs55703767), COL5A1 (rs7044529), and COL4A4 (rs2229813) variants with response to corneal collagen cross-linking (CXL) with riboflavin and ultraviolet A in patients with keratoconus (KC). METHODS: A total of 147 eligible patients with KC were genotyped for the specified collagen variants using real-time TaqMan-based polymerase chain reaction. Adjusted odds ratio (OR) with 95% confidence interval (CI) was applied to assess the strength of the association with response to CXL for a decrease in maximum keratometry and/or an increase in corneal thickness. RESULTS: Eighty-two patients (55.8%) had post-CXL successful outcomes. The overall analysis revealed that minor allele frequencies of COL4A3, COL5A1, and COL4A4 variants were 0.22, 0.22, and 0.38, respectively. The G/T genotype of the COL4A3 variant was more prevalent in the successful group (43%) compared with the failure group (23%) (P < 0.001). COL4A3 (rs55703767) was associated with a good response under heterozygote (OR: 2.19, 95% CI, 1.04-4.59, P < 0.001) and overdominant (OR: 2.59, 95% CI, 1.25-5.38, P = 0.008) models. By contrast, COL5A1 and COL4A4 variants were not associated with the effective response after CXL treatment. Interestingly, stratification analysis by sex revealed that CXL was more successful in female patients with KC under heterozygote (OR: 4.71, 95% CI, 1.74-12.75), dominant (OR: 3.16, 95% CI, 1.29-7.78), and overdominant (OR: 5.18, 95% CI, 1.92-13.95) models for COL4A3 (rs55703767) variant. CONCLUSIONS: The COL4A3 (rs55703767) variant, among other study variants, could be implicated in CXL riboflavin/ultraviolet A treatment response in patients with KC in the study population. Large-scale replication and follow-up studies in different ethnic groups are warranted.

Validation of the Diagnostic and Prognostic Values of ADAMTS5 and FSTL1 in Osteoarthritis Rat Model.

OBJECTIVE: Osteoarthritis (OA) is a global public health problem and a leading cause of morbidity and disability. Due to lack of sensitive and specific tools for early OA diagnosis and predicting prognosis, the availability of new reliable and sensitive biomarkers is a widely appreciated need to identify patients at risk for incident disease or disease progression. Accordingly, our study was conducted to validate the usefulness of disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and follistatin-like protein 1 (FSTL1) to achieve this goal. DESIGN: Fifty-four male Wistar rats were randomized into 3 groups; 24 rats were subjected to medial meniscal tear (MMT) surgery on the right knee joint (OA group), 24 rats were subjected to sham surgery (sham group), and 6 healthy rats (negative control group). Six animals from each group were sacrificed every 2 weeks. At each time point, the right knee joint of each animal was visualized radiologically, a blood sample was collected, and cartilage tissues were isolated for histopathological and western blot analysis. RESULTS: We found that the expression levels of ADAMTS5 and FSTL1 significantly increased with OA progression, especially at weeks 4, 6, and 8 after surgery. Notably, the serum levels of ADAMTS5 and FSTL1 showed significant positive correlations with each other and with the studied inflammatory markers. CONCLUSIONS: Our findings suggest that ADAMTS5 and FSTL1 can serve as important and informative serological markers of disease activity in OA. However, further research is needed to validate their use for improving the diagnosis and prognosis of OA in humans.