Efficacy and Safety of Ranibizumab Biosimilar QL1205 in Neovascular Age-related Macular Degeneration: A Phase 3 Randomized Trial.

OBJECTIVE: This study aimed to demonstrate the clinical equivalence of biosimilar QL1205 and reference ranibizumab, Lucentis®, in patients with neovascular age-related macular degeneration (nAMD). DESIGN: This was a multi-center, double-blinded, randomized controlled phase 3 trial. SUBJECTS, PARTICIPANTS, AND CONTROLS: Treatment-naïve patients with active nAMD were randomly assigned to receive QL1205 or reference ranibizumab. METHODS, INTERVENTION, OR TESTING: Patients received intravitreal injection of QL1205 or reference ranibizumab at a dose of 0.5 mg in the study eye once every four weeks for 48 weeks. MAIN OUTCOME MEASURES: The primary endpoint was change in best-corrected visual acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 8 compared to baseline level. Biosimilarity of QL1205 to reference ranibizumab was assessed with an equivalence range for the difference in BCVA letters between -3.49 and +3.49. RESULTS: Between June 27, 2019 and June 8, 2021, 616 patients were randomized to the QL1205 group (n=308) and the reference ranibizumab group (n=308). The mean improvement of BCVA was +6.3±9.13 ETDRS letters in the QL1205 group and +7.3±8.82 ETDRS letters in the reference ranibizumab group at week 8. Both the 90% confidence interval (CI) [-2.23, 0.13] and 95% CI [-2.46, 0.36] of the difference between the two treatment groups (P=0.1434) were within the predefined equivalence range. Safety profiles were manageable in both groups. CONCLUSIONS: QL1205 was biosimilar to reference ranibizumab regarding clinical efficacy, ocular and systemic safety, as well as immunogenicity and pharmacokinetics profiles in the treatment of patients with nAMD.

Metabolomic Disparities in Intraocular Fluid Across Varied Stages of Cataract Progression: Implications for the Analysis of Cataract Development.

Introduction: The lens's metabolic demands are met through a continuous circulation of aqueous humor, encompassing a spectrum of components such as organic and inorganic ions, carbohydrates, glutathione, urea, amino acids, proteins, oxygen, carbon dioxide, and water. Metabolomics is a pivotal tool, offering an initial insight into the complexities of integrated metabolism. In this investigative study, we systematically scrutinize the composition of intraocular fluid in individuals afflicted with cataracts. Methods: The investigation involved a comprehensive analysis of aqueous humor samples from a cohort comprising 192 patients. These individuals were stratified by utilizing the SPONCS classification system, delineating distinct groups characterized by the hardness of cataracts. The analytical approach employed targeted quantitative metabolite analysis using HILIC-based liquid chromatography coupled with high-resolution mass spectrometric detection. The metabolomics data analysis was performed with MetaboAnalyst 5.0. Results: The results of the enrichment analysis have facilitated the inference that the discerned disparities among groups arise from disruptions in taurine and hypotaurine metabolism, variations in tryptophan metabolism, and modifications in mitochondrial beta-oxidation of short-chain saturated fatty acids and pyrimidine metabolism. Conclusion: A decline in taurine concentration precipitates diminished glutathione activity, prompting an elevated requirement for NAD+ and instigating tryptophan metabolism along the kynurenine pathway. Activation of this pathway is additionally prompted by interferon-gamma and UV radiation, leading to the induction of IDO. Concurrently, heightened mitochondrial beta-oxidation signifies a distinctive scenario in translocating fatty acids into the mitochondria, enhancing energy production.

MERCURY-3: a randomized comparison of netarsudil/latanoprost and bimatoprost/timolol in open-angle glaucoma and ocular hypertension.

PURPOSE   : To compare the efficacy and safety of the fixed-dose combination (FDC) of netarsudil 0.02%/latanoprost 0.005% ophthalmic solution (NET/LAT; Roclanda®) with bimatoprost 0.03%/timolol maleate 0.5% (BIM/TIM; Ganfort®) ophthalmic solution in the treatment of open-angle glaucoma (OAG) and ocular hypertension (OHT). METHODS: MERCURY-3 was a 6-month prospective, double-masked, randomized, multicenter, active-controlled, parallel-group, non-inferiority study. Patients (≥ 18 years) with a diagnosis of OAG or OHT in both eyes that was insufficiently controlled with topical medication (IOP ≥ 17 mmHg in ≥ 1 eye and < 28 mmHg in both eyes) were included. Following washout, patients were randomized to once-daily NET/LAT or BIM/TIM for up to 6 months; efficacy was assessed at Week 2, Week 4, and Month 3; safety was evaluated for 6 months. Comparison of NET/LAT relative to BIM/TIM for mean IOP at 08:00, 10:00, and 16:00 h was assessed at Week 2, Week 6, and Month 3. Non-inferiority of NET/LAT to BIM/TIM was defined as a difference of ≤ 1.5 mmHg at all nine time points through Month 3 and ≤ 1.0 mmHg at five or more of nine time points through Month 3. RESULTS: Overall, 430 patients were randomized (NET/LAT, n = 218; BIM/TIM, n = 212), and all received at least one dose of study medication. Efficacy analyses were performed at Month 3 on 388 patients (NET/LAT, n = 184; BIM/TIM, n = 204). NET/LAT demonstrated non-inferiority to BIM/TIM, with a between-treatment difference in IOP of ≤ 1.5 mmHg achieved at all time points and ≤ 1.0 mmHg at the majority of time points (six of nine) through Month 3. Mean diurnal IOP during the study ranged from 15.4 to 15.6 mmHg and 15.2 to 15.6 mmHg in the NET/LAT and BIM/TIM groups respectively, with no between-group statistically significant difference. No significant differences were observed in key secondary endpoints. No serious, treatment-related adverse events (AEs) were observed, and AEs were typically mild/moderate in severity. The most common treatment-related AEs were conjunctival hyperemia (NET/LAT, 30.7%; BIM/TIM, 9.0%) and cornea verticillata (NET/LAT, 11.0%; BIM/TIM, 0%). CONCLUSIONS: Once-daily NET/LAT was non-inferior to BIM/TIM in IOP reduction in OAG and OHT, with AEs consistent with previous findings. NET/LAT offers a compelling alternative FDC treatment option for OAG and OHT.

Microstructural Changes in the Macula Following Cataract Surgery in Patients with Type 2 Diabetes Mellitus Detected Using Optical Coherence Tomography Angiography.

BACKGROUND: Ophthalmologists treat diabetic macular edema before cataract surgery to reduce possible complications. Despite improvements in diagnostic techniques, whether cataract surgery per se causes the progression of diabetic retinopathy with macular edema remains unclear. This study aimed to evaluate the impact of phacoemulsification on the central retina and its correlation with diabetes compensation as well as changes in the retina before surgery. METHODS: Thirty-four type 2 diabetes mellitus patients who underwent phacoemulsification cataract surgery were included in this prospective longitudinal study. Of them, 29.4% had macular edema before surgery, and 70.6% had a normal macular structure. All patients underwent ophthalmic examinations, including optical coherence tomography angiography, at baseline and at one and three months after surgery. The Mann-Whitney test was performed to compare the area of the foveal avascular zone, perimeter of the foveal avascular zone, and mean vascular density in the para- and perifoveal deep and superficial capillary plexuses. All parameters were measured before and at one and three months after surgery. Multiple linear regression models with adjustments for glycated hemoglobin and duration of diabetes mellitus were constructed to assess the association between the area of the foveal avascular zone and diabetic macular edema. RESULTS: Significant differences in the area of the foveal avascular zone, perimeter of the foveal avascular zone, and perifoveal density in the deep capillary plexus were observed at all three time points. In the fully adjusted linear regression model, those without diabetic macular edema had a reduced probability for changes in the foveal avascular zone at one and three months after surgery (effect estimate ß = -0.20 [95% CI -0.31; -0.09] and ß = -0.13 [-0.22; -0.03] for one and three months, respectively) compared with those with diabetic macular edema. CONCLUSIONS: Cataract surgery itself does not cause significant and permanent increase in diabetic macular edema three months post-surgery. On the contrary, in a group with diabetic macular edema before the surgery, central retinal thickness tended to stabilize three months after surgery. If the duration of diabetes is shorter and diabetes is better compensated, the possibility of changes in the foveal avascular zone is reduced.

Isolated posterior capsule rupture after blunt eye injury.

Isolated posterior capsule rupture of the crystalline lens after blunt eye injury is a rare complication and demands a special surgical management strategy in order to achieve a good visual outcome.

Anterior Capsule Opening Contraction and Late Intraocular Lens Dislocation after Cataract Surgery in Patients with Weak or Partially Absent Zonular Support.

BACKGROUND AND OBJECTIVES: To evaluate anterior capsule opening (ACO) contraction and late intraocular lens (IOL) dislocation after cataract surgery in patients with weak or partially absent zonular support and assess methods of reducing these complications. MATERIALS AND METHODS: For this prospective study, we enlisted cataract surgery patients in our hospital with preoperative diagnoses of weak zonules. All patients received phacoemulsification surgery with implantation of a hydrophobic acrylic IOL and capsular tension ring (CTR). ACO reductions were measured for six months after enrolment. Data on late IOL dislocations were collected five years after enrolment of the last patient. RESULTS: Fifty-three patients were enrolled from 2011 to 2015. Over the six-month active follow-up period, ACO area reduction was 23% in patients receiving CTRs of 11 mm diameter and 8% for patients with CTRs of 12 mm, with an overall mean of 15% reduction. Five years after the last patient was enrolled, seven patients (13%) had experienced late IOL-CTR-capsular bag dislocation. For these patients, the mean ACO reduction in the first six months of follow-up was 33%, including for those who had received neodymium-doped yttrium aluminum garnet (Nd: YAG) anterior capsulotomies. CONCLUSION: Use of hydrophobic acrylic lenses and CTR reduces ACO contraction, with rates comparable to those after cataract surgery without ocular comorbidity. Our patients experienced a relatively high rate of late IOL-CTR-capsular bag dislocation. However, dislocated complexes were easily repositioned and few patients required IOL exchange. Frequent visits are warranted to promptly detect late complications of cataract surgery in patients with weak zonular support.

Corneal Perforation Self-Healing with an Iris Plug in the Cornea.

Keratitis treatment outcome is usually dependent on the targeted treatment of the cause. We want to present a small corneal ulcer of unidentified origin that progressed into corneal melting and resulted in corneal perforation. The patient had a widespread antibacterial and fungal treatment and an ophthalmological follow-up with slit-lamp examination and AS-OCT. The spontaneous iris plug in the cornea helped to solve the anterior chamber collapse and made permanent anatomical changes in the anterior part. A 45-week follow-up found a hyperdense stromal corneal scar with 556-µm-wide stable iris-cornea contact and BCVA of 0.8. As a result, an iris plug in the cornea after corneal perforation can have a positive effect on healing and lead to good visual outcome.

Long-Term Outcome of Cataract Surgery in Eyes with Pseudoexfoliation Syndrome Associated with Weak Zonules: A Case Report.

A cataract surgery in both eyes was scheduled for an 81-year-old female patient. However, ophthalmic examination revealed marked iridodonesis, phacodonesis and pseudoexfoliative material on the surface of the lens in both eyes indicating weak zonules caused by pseudoexfoliation syndrome, which was more pronounced in the left eye. Cataract surgery was performed initially in the left eye by phacoemulsification. Additionally, iris hooks and capsular tension ring (CTR) were used to stabilize the capsular bag, and the haptic of the intraocular lens (IOL) was sutured to the iris at the end of the surgery. The same procedure except haptic suturing was performed in the right eye after 6 months. The left eye remained stable, whereas the right eye developed considerable anterior capsular contraction 2 months postoperatively. Neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy was performed to treat the condition. Moreover, 3 years after the initial surgery, late IOL-CTR-capsular-bag complex dislocation developed in the right eye, and reposition surgery was performed. Three days after IOL-CTR-capsular-bag complex reposition surgery, endophthalmitis developed; the eye responded well to 1 mg intravitreal vancomycin treatment. IOL in the right eye remained stable 3 years postoperatively.

Factors influencing myopic shift in children after intraocular lens implantation.

INTRODUCTION: Intraocular lenses have always been a controversial topic in pediatric cataract surgery. In the early 1990s in the post-Soviet states of Eastern Europe, intraocular lenses promised an easier full-time correction and amblyopia treatment. Since 1991, ophthalmologists in Latvia have been implanting intraocular lenses in infants. Amount of the postoperative myopic shift and its influencing factors, analyzed in this article, are important indicators of congenital cataract treatment. MATERIALS AND METHODS: A retrospective chart review off 85 children (137 eyes) who underwent foldable posterior chamber intraocular lens implantation at the Clinical University Hospital in Riga, Latvia, from 1 January 2006 until 31 December 2016, was performed. Depending on the age at surgery, patients were divided into six groups: 1-6, 7-12, 13-24, 25-48, 49-84, and 85-216 months. RESULTS: The largest and more variable myopic shift was found in a group of diffuse/total and nuclear cataract with surgery before the age of 6 months. There was a statistically significant correlation between the acquired best-corrected visual acuity and the amount of myopic shift (rs = 0.33; p < 0.001). Comparing the amount of myopic shift in two groups of different intraocular lens implantation target refraction tactics, we did not find statistically significant differences. Comparing the amount of myopic shift and implanted intraocular lens power, a negative, statistically significant correlation was found. CONCLUSION: The earlier the cataract extraction surgery and intraocular lens implantation is performed, the larger the myopic shift. The morphological type of cataract, best-corrected visual acuity, secondary glaucoma, and intraocular lens power influence the amount of myopic shift.

Tear osmolarity after cataract surgery.

PURPOSE: To evaluate the changes in tear film osmolarity and Schirmer I test after cataract surgery. METHODS: This single-center, prospective study included patients with no subjective complaints about dry eye disease. Patients with the following conditions were excluded: contact lens wearers, patients with diabetes, pseudoexfoliation, pterygia, and eye drops users. The eye that had not undergone surgery was considered the control group. Tear osmolarity and Schirmer I test were evaluated before surgery and during the first postoperative month. RESULTS: Thirty-seven patients were enrolled in the study. Before surgery, tear osmolarity was 301.2 ± 15.09 Osm/L in the study group and 302.3 ± 14.21 mOsm/L in the control group (P = 0.2), while Schirmer I test averaged 13.4 ± 10.50 mm in the study group and 13.7 ± 10.79 mm in the control group (P = 0.6). The next morning, the tear osmolarity decreased to <275 mOsm/L in the study group while in the control group, the value increased to 303.1 mOsm/L ± 13.68 (P = 0.008). The Schirmer I test in the same morning showed an increase up to 19.9 ± 9.73 mm in the study group and to 15.7 ± 10.19 mm in the control group (P = 0.01). One week later, the tear osmolarity increased to 311.8 ± 14.85 mOsm/L, while the control group averaged 301.7 ± 11.84 mOsm/L (P = 0.013). The Schirmer I test results decreased to 15.8 ± 9.37 mm in the study group and 13.9 ± 10.19 mm in the control group (P = 0.07) one week after the surgery. One month after surgery, tear osmolarity and Schirmer I test results in the study group decreased to the control group level (P > 0.05). CONCLUSIONS: The tear osmolarity results increased to the dry eye disease level in the first postoperative week. Over the course of one month, the difference in tear osmolarity and Schirmer I test values for the study and control groups leveled off.

Anterior capsulorhexis opening reduction after cataract surgery with subluxated lenses.

BACKGROUND AND OBJECTIVE: This study sought to evaluate anterior capsulorhexis opening (ACO) reductions after surgery for a subluxated lens. Significant reduction of an ACO supports direct zonular involvement (capsular factors excluded by use of capsular tension rings [CTRs] and modern intraocular lens [IOLs]), and these findings question the long-term efficacy of subluxated lens surgery by means of cataract surgery. A small ACO due to lens mobility, non-enlargement of the ACO, and no lens epithelial cell washing due to an additional risk of further zonular damage were left as additional features to evaluate the possible outcomes of this simplified but still complicated surgery. MATERIALS AND METHODS: Data from 30 patients were used in the final analysis of this prospective study. Phacoemulsifications of subluxated lenses were performed in all patients, and iris/capsule hooks and CTRs or Cionni rings were used as stabilisers of the lens. Photography of the anterior parts (performed at 1 day, 1 week, 1 month, 3 months and 6 months after surgery) was used to evaluate the anterior capsulorhexis openings. RESULTS: Small initial anterior capsulorhexis openings (13.54mm2) were achieved, and the area reduction at 6 months was 16.70% (mean area at month 6: 11.28mm2, P<0.001). The reduction of the ACO area in the pseudoexfoliation (PEX) syndrome patients was 20% relative to the initial size (13.49mm2 vs. 10.92mm2, P<0.001). Two patients exhibited marked ACO reductions, and both were referred for anterior laser capsulotomy treatment. CONCLUSIONS: A weak or partially absent zonule does not markedly affect the reduction of the anterior capsule opening if appropriate surgical techniques, support materials and IOLs are used, even in the presence of a small initial capsulorhexis opening area. Therefore, a cataract surgery approach on the subluxated lens should be used. Ocular comorbidities, particularly PEX syndrome, play more significant roles in ACO reduction, and appropriate ACO size reducing inhibitors (e.g., anterior laser capsulotomy) or other types of surgery should be used.

Association of NT-proANP Level in Plasma and Humor Aqueous with Primary Open-Angle Glaucoma.

PURPOSE: The aim of this study is to determine differences in the levels of NT-proANP in the plasma and aqueous humor of glaucoma and cataract patients and to evaluate whether any relationships are present. METHODS: The study group consisted of 58 patients with primary-open glaucoma (POAG) undergoing trabeculectomy surgery. The control group was comprised of 32 age-matched cataract patients. The concentration of the N-terminal fragment of the proatrial natriuretic peptide (NT-proANP, 1-98) in the aqueous humor and blood plasma samples was measured using an immunochemical method (ELISA). RESULTS: The plasma NT-proANP concentration was significantly increased in patients with POAG compared to that in the control group (7.00 vs. 4.65 nmol/L, P = 0.0054). Similarly, the NT-proANP concentration in the aqueous humor was significantly higher in the POAG patients (0.47 vs. 0.09 nmol/L, P = 0.0112). However, there was no correlation between the NT-proANP values in the aqueous humor and the plasma of the POAG patients, as well as between the NT-proANP values in the aqueous humor and the intraocular pressure. CONCLUSIONS: We identified an association between the levels of NT-proANP in the plasma and the aqueous humor with POAG. Our data support the idea of the involvement of NP system in the development of POAG and highlight ANP as a possible biomarker of glaucoma.

Twice-daily brinzolamide/brimonidine fixed combination versus brinzolamide or brimonidine in open-angle glaucoma or ocular hypertension.

PURPOSE: To compare the intraocular pressure (IOP)-lowering efficacy and safety of brinzolamide 1% and brimonidine 0.2% fixed combination (BBFC) with that of brinzolamide 1% or brimonidine 0.2% monotherapy, all dosed 2 times per day (BID). DESIGN: Six-month, phase 3, randomized, multicenter, double-masked clinical trial. PARTICIPANTS: A total of 560 patients with primary open-angle glaucoma or ocular hypertension who had insufficient IOP reduction with their current therapeutic regimen or who were receiving ≥ 2 IOP-lowering medications. INTERVENTION: Patients received BBFC (n = 193), brinzolamide 1% (n = 192), or brimonidine 0.2% (n = 175) BID. MAIN OUTCOME MEASURES: The primary end point was mean change in diurnal IOP from baseline to month 3. Supportive end points included mean diurnal IOP change from baseline at week 2, week 6, and month 6; and mean IOP, mean IOP change from baseline, mean percentage IOP change from baseline, and percentage of patients with IOP <18 mmHg at week 2, week 6, month 3, and month 6 at each assessment time point (i.e., 9 am, 11 am, and 4 pm). Adverse events were recorded throughout the study. RESULTS: Baseline diurnal IOP was similar among groups (mean ± standard deviation: BBFC, 25.9 ± 0.19 mmHg; brinzolamide, 25.9 ± 0.20 mmHg; brimonidine, 26.0 ± 0.19 mmHg). At month 3, BBFC lowered mean diurnal IOP from baseline to a significantly greater extent than brinzolamide (least squares [LS] mean difference: -1.4 mmHg; P < 0.0001; t test) and brimonidine (LS mean difference: -1.5 mmHg; P < 0.0001). All supportive end points corroborated the results of the primary efficacy analysis. Mean percentage reductions in IOP from baseline were 26.7% to 36.0% with BBFC, 22.4% to 27.9% with brinzolamide, and 20.6% to 31.3% with brimonidine. The most common adverse drug reactions were ocular side effects, including hyperemia, blurred vision, allergic-type reactions, and discomfort. The incidence of hyperemia of the eye was slightly lower with brinzolamide than with BBFC and brimonidine, whereas blurred vision and ocular discomfort were slightly more common with BBFC than with brinzolamide or brimonidine. CONCLUSIONS: Brinzolamide 1% and brimonidine 0.2% fixed combination administered BID had a significantly greater IOP-lowering effect than either brinzolamide or brimonidine alone and displayed a safety profile consistent with its individual components.

RADIANCE: a randomized controlled study of ranibizumab in patients with choroidal neovascularization secondary to pathologic myopia.

OBJECTIVE: To compare the efficacy and safety of ranibizumab 0.5 mg, guided by visual acuity (VA) stabilization or disease activity criteria, versus verteporfin photodynamic therapy (vPDT) in patients with visual impairment due to myopic choroidal neovascularization (CNV). DESIGN: Phase III, 12-month, randomized, double-masked, multicenter, active-controlled study. PARTICIPANTS: Patients (N = 277) with visual impairment due to myopic CNV. METHODS: Patients were randomized to receive ranibizumab on day 1, month 1, and thereafter as needed guided by VA stabilization criteria (group I, n = 106); ranibizumab on day 1 and thereafter as needed guided by disease activity criteria (group II, n=116); or vPDT on day 1 and disease activity treated with ranibizumab or vPDT at investigators' discretion from month 3 (group III, n = 55). MAIN OUTCOME MEASURES: Mean average best-corrected visual acuity (BCVA) change from baseline to month 1 through months 3 (primary) and 6, mean BCVA change and safety over 12 months. RESULTS: Ranibizumab treatment in groups I and II was superior to vPDT based on mean average BCVA change from baseline to month 1 through month 3 (group I: +10.5, group II: +10.6 vs. group III: +2.2 Early Treatment Diabetic Retinopathy Study [ETDRS] letters; both P<0.0001). Ranibizumab treatment guided by disease activity was noninferior to VA stabilization-guided retreatment based on mean average BCVA change from baseline to month 1 through month 6 (group II: +11.7 vs. group I: +11.9 ETDRS letters; P<0.00001). Mean BCVA change from baseline to month 12 was +13.8 (group I), +14.4 (group II), and +9.3 ETDRS letters (group III). At month 12, 63.8% to 65.7% of patients showed resolution of myopic CNV leakage. Patients received a median of 4.0 (group I) and 2.0 (groups II and III) ranibizumab injections over 12 months. No deaths or cases of endophthalmitis and myocardial infarction occurred. CONCLUSIONS: Ranibizumab treatment, irrespective of retreatment criteria, provided superior BCVA gains versus vPDT up to month 3. Ranibizumab treatment guided by disease activity criteria was noninferior to VA stabilization criteria up to month 6. Over 12 months, individualized ranibizumab treatment was effective in improving and sustaining BCVA and was generally well tolerated in patients with myopic CNV.

Point mutations associated with Leber hereditary optic neuropathy in a Latvian population.

PURPOSE: To study mutations associated with Leber hereditary optic neuropathy (LHON) in patients suspected of having this mitochondrial disorder in a Latvian population. Additional aims were to determine the heteroplasmy status of all non-synonymous polymorphisms identified in the current study and to identify the mitochondrial haplogroups of the studied participants because these factors may contribute to the manifestation of LHON. METHODS: Twelve patients, including patients in two families, were enrolled in the current study. LHON was suspected based on the findings of ophthalmologic examinations. In clinically affected individuals, the presence of all previously reported LHON-associated mutations was assessed with sequencing analysis. Additionally, the SURVEYOR endonuclease assay was used to detect heteroplasmy. The mitochondrial haplogroups were identified with restriction analysis and the sequencing of hypervariable segment 1. RESULTS: In one family (mother and son), there was one primary LHON-associated mutation, G11778A. In addition, one rare previously reported LHON-associated polymorphism, A13637G, was detected in two unrelated patients. A non-synonymous polymorphism at T6253C was found in one individual. This mutation was reported in the background of the 3460 mutation among LHON patients in a Chinese population. No non-synonymous point mutations in mitochondrial DNA were found in five of the study participants. CONCLUSIONS: Molecular analysis of 12 patients with suspected LHON confirmed the diagnosis in four patients and allowed the use of appropriate prophylactic measures and treatment. Further investigations and additional studies of different populations are necessary to confirm the role of the non-synonymous polymorphisms A13637G and T6253C in the manifestation of LHON and the associations of these polymorphisms with mitochondrial haplogroups and heteroplasmy.

Evaluation of axonal optic nerve damage using visual evoked potentials and optical coherence tomography in patients with multiple sclerosis.

BACKGROUND AND OBJECTIVE: Axonal tissue impairment plays a substantial role in the development of disability in multiple sclerosis. The aim of our study was to analyze the clinical utility of visual evoked potentials (VEP) and optical coherence tomography (OCT) in the diagnosis of optic nerve axonal damage and to determine the correlation between the retinal nerve fiber layer at the temporal quadrant (RNFLT) thickness and the VEP amplitude in multiple sclerosis patients with and without a history of acute optic neuritis (ON). MATERIAL AND METHODS: This cross-sectional study included 69 relapsing-remitting patients with multiple sclerosis from Pauls Stradins Clinical University Hospital, who were divided into 2 groups: with and without a history of ON. The RNFLT thickness and the VEP amplitude were measured. RESULTS. A total of 25 clinically affected eyes were studied. VEP showed a higher sensitivity (64%) than OCT (50%) in supporting a clinical diagnosis of ON. A significant correlation was found between the RNFLT thickness in the temporal segment and the average VEP amplitude both in the eyes of MS patients with (rs=0.42, P=0.01) and without a history of ON (rs=0.44, P<0.001). CONCLUSIONS: The evidence from this study suggests that diagnostics of optic nerve axonal damage is feasible by means of using the average VEP amplitude instead of OCT alone. However, the combination of VEP and OCT increases the chance to confirm the existence of ON. A significant correlation was found between structural and functional vision parameters for both patients with and without a history of ON.

A multicenter, double-blind, parallel group, placebo-controlled clinical study to examine the safety and efficacy of T-Clair SPHP700-3 in the management of mild to moderate dry eye in adults.

PURPOSE: To study the safety and efficacy of T-Clair SPHP700-3, a new over-the-counter preservative-free formulation, in the management of mild to moderate dry eye in adults. METHODS: Sixty adult patients with mild to moderate dry eye were consecutively recruited in 2 eye clinics and randomized into 2 groups: treatment and placebo. Signs and symptoms of dry eye were compared along 28 days of treatment. RESULTS: No adverse events were reported during the study. Symptoms and signs of dry eye showed significant differences between the 2 groups after 2 and 4 weeks of treatment. CONCLUSIONS: SPHP700-3 preservative-free formulation showed to be safe and effective in mild to moderate dry eye, improving tear film stability, ocular surface lubrification, and patients' symptomatology.

Efficacy and safety of travoprost/timolol vs dorzolamide/timolol in patients with open-angle glaucoma or ocular hypertension.

PURPOSE: To compare the intraocular pressure- (IOP-) lowering efficacy of fixed combinations travoprost 0.004%/timolol 0.5% and dorzolamide 2%/timolol 0.5% in patients with ocular hypertension or open-angle glaucoma. METHODS: In this prospective, multicenter, double-masked, randomized clinical trial, 319 qualifying patients received either travoprost/timolol once daily in the morning (n = 157) or dorzolamide/timolol twice daily (n = 162). IOP was assessed morning and evening at 2 and 6 weeks. The primary outcome measure was mean diurnal IOP. RESULTS: Baseline mean IOP values were similar between groups. Mean pooled diurnal IOP was significantly lower in the travoprost/timolol group (16.5 mmHg +/- 0.23) than in the dorzolamide/timolol group (17.3 mmHg +/- 0.23; P = 0.011). Mean IOP was significantly lower in the travoprost/timolol group compared to the dorzolamide/timolol group at the 9 AM time point both at Week 2 (P = 0.006) and Week 6 (P = 0.002). The travoprost/timolol combination produced mean IOP reductions from baseline of 35.3% to 38.5%, while the dorzolamide/timolol combination produced mean IOP reductions from baseline of 32.5% to 34.5%. CONCLUSIONS: The fixed combination travoprost 0.004%/timolol 0.5% dosed once daily in the morning demonstrated superior mean diurnal IOP-lowering efficacy compared to dorzolamide 2%/timolol 0.5% dosed twice daily in patients with ocular hypertension or open-angle glaucoma.

The safety and efficacy of brinzolamide 1%/timolol 0.5% fixed combination versus dorzolamide 2%/timolol 0.5% in patients with open-angle glaucoma or ocular hypertension.

PURPOSE: This study compared the intraocular pressure (IOP)-lowering efficacy of 2 fixed combination products, brinzolamide 1%/timolol 0.5% suspension (Azarga, Brinz/Tim) and dorzolamide 2%/timolol 0.5% solution (Dorz/Tim), in patients with open-angle glaucoma or ocular hypertension who required a change in therapy due to elevated IOP while receiving IOP-lowering medication. METHODS: This was a one-year, multicenter, randomized, double-masked, active-controlled, parallel-group trial of Brinz/Tim and Dorz/Tim. IOP assessments were taken at 8 and 10 AM at week 2 and months 3 and 9, and at 8 AM, 10 AM, and 4 PM at months 6 and 12. Primary efficacy was a noninferiority comparison of mean IOP at the three month 6 time points. RESULTS: Of the 437 patients enrolled, 220 dosed Brinz/Tim whereas 217 dosed Dorz/Tim twice daily. Brinz/Tim produced IOP-lowering efficacy comparable to Dorz/Tim, with the upper 95% confidence limits for the differences between groups within +1.5 mm Hg at all assessment times, including the month 6 primary efficacy time points, establishing noninferiority. Differences in means numerically favored Brinz/Tim at 9 of 12 study visits and times. The IOP reductions ranged from 7.2 to 9.2 mm Hg for Brinz/Tim and from 7.4 to 8.9 mm Hg for Dorz/Tim. Although a similar overall safety profile was observed between the 2 treatment groups, Brinz/Tim showed significantly less ocular irritation (2.7% vs. 10.6%; P=0.0009) than Dorz/Tim. CONCLUSIONS: Brinz/Tim suspension provides statistically significant and clinically relevant IOP-lowering efficacy that is noninferior to Dorz/Tim. Additionally, Brinz/Tim affords an ocular comfort advantage compared with Dorz/Tim.