[Femtosecond laser-assisted keratoplasty]. / Femtoszekundumlézeres keratoplasztika.

INTRODUCTION AND AIM: To present our results on femtosecond laser-assisted penetrating keratoplasty. PATIENTS AND METHOD: Twenty-five eyes of 25 patients underwent surgery with the following indications: pseudophakic bullous keratopathy (n = 10), keratoconus (n = 4), corneal dystrophy (n = 5), corneal scar (n = 4), band keratopathy (n = 2). Trephination of both the donor and recipient corneas were performed with VisuMax femtosecond laser device (Carl Zeiss Meditec AG, Jena, Germany). In each case, trephinaton of the donor tissue was performed first with an artificial anterior chamber (Moria, Antony, France). For the surgical plan and in the postoperative period we obtained different corneal imaging modalities. The corneal power was measured with corneal topography (TMS-4, Tomey, Nürnberg, Germany) and Scheimpflug tomography (Pentacam HR, Oculus, Wetzlar, Germany). The central corneal thickness was evaluated with Pentacam and corneal endothelial cell density was measured with specular microscopy (SP3000P, Topcon, Tokyo, Japan). The corneal structure was imaged with anterior segment optical coherence tomography (Visante, Carl Zeiss Meditec AG). All measurements were performed every 3 months in the first year and yearly thereafter. The follow-up period was 3 years in every case. RESULTS: The corrected decimal visual acuity showed an improvement from a preoperative 0.1 ± 0.1 to a postoperative 0.71 ± 0.18 value at the end of the follow-up period (p = 0.03). All corneal grafts maintained their transparency, there were no immunological rejection during the follow-up. Topographical astigmatism was 4.5 ± 3.1 D in the first month; it showed a decreasing tendency, but there was no significant change in the 3-year period. The mean central corneal thickness changed with 60 µm during the follow-up; there was no significant difference between the first month (564 ± 52 µm) and the third year (596 ± 64 µm) mean pachymetry values (p = 0.1). The mean endothelial cell density decreased first, then remained stable, but did not change significantly from the first (1641 ± 433 cells/mm2) to the last postoperative visit (1220 ± 391 cells/mm2, p = 0.1). CONCLUSIONS: In the case of femtosecond laser-assisted penetrating keratoplasty, trephination of the donor and recipient cornea is performed automatically in a highly precise fashion. The accurate cutting surface provides excellent wound apposition and healing. Both anatomical and functional rehabilitation of patients undergoing surgery are favourable and fast. Orv Hetil. 2018; 159(17): 671-676.

Treat-and-Extend versus Monthly Regimen in Neovascular Age-Related Macular Degeneration: Results with Ranibizumab from the TREND Study.

PURPOSE: To evaluate the efficacy and safety of ranibizumab 0.5 mg treat-and-extend (T&E) versus monthly regimens in patients with neovascular age-related macular degeneration (nAMD) from the TReat and extEND (TREND) study. DESIGN: A 12-month phase 3b visual acuity (VA) assessor-masked, multicenter, randomized, interventional study. PARTICIPANTS: Six hundred fifty patients. METHODS: Treatment-naïve nAMD patients (age, ≥50 years) were randomized 1:1 to receive either a ranibizumab 0.5 mg T&E (n = 323) or monthly (n = 327) regimen. MAIN OUTCOMES MEASURES: The primary objective was to show noninferiority of ranibizumab 0.5 mg T&E versus monthly regimen, as assessed by the change in best-corrected VA (BCVA) from baseline to the end of the study. Secondary objectives included change in retinal central subfield thickness (CSFT) from baseline to the end of study, treatment exposure, and safety. RESULTS: Overall, 89.8% (T&E) and 90.2% (monthly) of patients completed the study. Patient demographic and baseline characteristics were well balanced between the 2 treatment groups. The T&E regimen was noninferior (P < 0.001) to the monthly regimen, with a least squares mean BCVA change from baseline of 6.2 versus 8.1 letters to the end of study, respectively. In both treatment groups, most BCVA improvements occurred during the first 6 months and were maintained until the end of the study. The mean change in CSFT from baseline to the end of study was -169.2 µm and -173.3 µm in the T&E and monthly groups, respectively. Fewer injections were required in patients receiving the T&E (8.7) versus monthly (11.1) regimen, with mean number of postbaseline visits of 8.9 and 11.2, respectively. Types and rates of adverse events were comparable between the treatment groups. CONCLUSIONS: Ranibizumab 0.5 mg administered according to a T&E regimen was statistically noninferior and clinically comparable with a monthly regimen in improving VA from baseline to the end of study. No new safety signals for ranibizumab were identified.

Plasminogen activator activity in tears of pregnant women.

PURPOSE: Plasminogen activator activity (PAA) in tears of pregnant women was investigated at various gestation times to assess the availability of plasminogen activator for aiding potential corneal wound healing processes during pregnancy. METHODS: PAA was measured by a spectrophotometric method. The analysis used 91 tear samples from pregnant and non-pregnant women, supplemented with 10 additional tear PAA measurements from non-pregnant women obtained in a previous study. RESULTS: Tear levels of PAA in pregnant women formed a bimodal distribution. Either the tear PAA level was zero or non-zero during pregnancy. When non-zero, the tear PAA level was dissociated from gestation time and not different than non-pregnant and post-pregnant levels. The frequency of occurrence of zero level tear PAA increased with gestation: 16%, 17% and 46% had zero tear PAA in samples taken from women in the first, second and third trimester, respectively. CONCLUSIONS: Overall, of the tear samples taken from women during pregnancy, a total of 26% were at zero tear PAA. The remaining tear samples had non-zero tear PAA values throughout gestation equivalent to non-pregnant tear PAA values, suggesting local control of the source of PAA in tears. Given the importance of the plasminogen activator system in tears to wound healing in the cornea, and the high occurrence of zero tear PAA in our sample of pregnant women, elective corneal surgery would be contraindicated. If corneal surgery is nevertheless necessary, the tear PAA level would be worth checking and patients with low level should be closely observed during the postoperative period.

Vascular Endothelial Growth Factor in Tear Samples of Patients with Systemic Sclerosis.

BACKGROUND: Systemic sclerosis is an autoimmune disease, characterized by widespread small vessel vasculopathy, immune dysregulation with production of autoantibodies, and progressive fibrosis. Changes in levels of proangiogenic cytokines had already been determined largely in serum. Our aim was to assess the levels of VEGF in human tears of patients with SSC. PATIENTS AND METHODS: Forty-three patients (40 female and 3 men, mean (SD) age 61 (48-74) years) with SSc and 27 healthy controls were enrolled in this study. Basal tear sample collection and tear velocity investigations were carried out followed by an ophthalmological examination. Total protein concentrations and VEGF levels were determined in tear samples. RESULTS: The average collected tear fluid volume developed 10.4 µL (1.6-31.2) in patients and 15.63 µL (3.68-34.5) in control subjects. The average total protein level was 6.9 µg/µL (1.8-12.3) in tears of patients and control tears contained an average of 4.132 µg/µL (0.1-14.1) protein. In patients with SSc the average concentration of VEGF was 4.9 pg/µL (3.5-8.1) and 6.15 pg/µL (3.84-12.3) in healthy samples. CONCLUSIONS: Total protein production was increased because of the smaller tear volume. Decreased VEGF in tear of SSc patients can be explained also by the decreased tear secretion of patients.

Combined Methods for Diabetic Retinopathy Screening, Using Retina Photographs and Tear Fluid Proteomics Biomarkers.

Background. It is estimated that 347 million people suffer from diabetes mellitus (DM), and almost 5 million are blind due to diabetic retinopathy (DR). The progression of DR can be slowed down with early diagnosis and treatment. Therefore our aim was to develop a novel automated method for DR screening. Methods. 52 patients with diabetes mellitus were enrolled into the project. Of all patients, 39 had signs of DR. Digital retina images and tear fluid samples were taken from each eye. The results from the tear fluid proteomics analysis and from digital microaneurysm (MA) detection on fundus images were used as the input of a machine learning system. Results. MA detection method alone resulted in 0.84 sensitivity and 0.81 specificity. Using the proteomics data for analysis 0.87 sensitivity and 0.68 specificity values were achieved. The combined data analysis integrated the features of the proteomics data along with the number of detected MAs in the associated image and achieved sensitivity/specificity values of 0.93/0.78. Conclusions. As the two different types of data represent independent and complementary information on the outcome, the combined model resulted in a reliable screening method that is comparable to the requirements of DR screening programs applied in clinical routine.

Repeatability data and agreement of keratometry with the VERION system compared to the IOLMaster.

PURPOSE: To analyze the repeatability of keratometric and white-to-white (WTW) distance measurements with the VERION Measurement Module (Alcon Laboratories, Inc., Fort Worth, TX) and to compare the measured data to the results of the IOLMaster (Carl Zeiss Meditec, Jena, Germany). METHODS: Three images were captured with the VERION and the flattest and steepest keratometric data, the astigmatism axis, and the WTW distance were recorded. Subsequently, the axial length, the keratometric data with axis, and the WTW distance were measured with an IOLMaster. The repeatability data of the keratometric value of the VERION System, converted to cross cylinder J0 and J45 vector components, were analyzed. The agreement data for keratometry obtained by the VERION System and the differences regarding keratometric data and WTW distance compared to IOLMaster were calculated. RESULTS: The measurements were conducted in 50 eyes of 50 healthy volunteers (median age: 50.32 years, range: 19.34 to 85.3 years). The flattest and the steepest keratometric data, the diopter of astigmatism, the J0 and J45 vector components, and WTW distance did not differ significantly between devices (P > .05). Intraclass correlation coefficients (range: 0.863 to 0.994) and Cronbach's alpha values (range: 0.950 to 0.998) were high for all parameters measured by the VERION System. CONCLUSIONS: The VERION System has high repeatability and agreement with the IOLMaster, making it suitable as an alternative tool in clinical practice.

A novel proteotoxic stress associated mechanism for macular corneal dystrophy.

Macular corneal dystrophy is a rare autosomal recessive eye disease affecting primarily the corneal stroma. Abnormal accumulation of proteoglycan aggregates has been observed intra- and extracellularly in the stromal layer. In addition to the stromal keratocytes and corneal lamellae, deposits are also present in the basal epithelial cells, endothelial cells and Descemet's membrane. Misfolding of proteins has a tendency to gather into aggregating deposits. We studied interaction of molecular chaperones and proteasomal clearance in macular dystrophy human samples and in human corneal HCE-2 epithelial cells. Seven cases of macular corneal dystrophy and four normal corneal buttons collected during corneal transplantation were examined for their expression patterns of heat shock protein 70, ubiquitin protein conjugates and SQSTM1/p62. In response to proteasome inhibition the same proteins were analyzed by western blotting. Slit-lamp examination, in vivo confocal cornea microscopy and transmission electron microscopy were used for morphological analyses. Heat shock protein 70, ubiquitin protein conjugates and SQSTM1/p62 were upregulated in both the basal corneal epithelial cells and the stromal keratocytes in macular corneal dystrophy samples that coincided with an increased expression of the same molecules under proteasome inhibition in the HCE-2 cells in vitro. We propose a novel regulatory mechanism that connects the molecular chaperone and proteasomal clearance system in the pathogenesis of macular corneal dystrophy.

Evaluation of posterior astigmatism measured with Scheimpflug imaging.

PURPOSE: Our aim was to assess the corneal power, axis, and age dependence of the anterior and posterior corneal surfaces with Scheimpflug imaging. METHODS: Patients older than 10 years without a history of ocular surgery, corneal diseases, contact lens wearing, or severe dry eye were enrolled. Data regarding the anterior and posterior cornea were analyzed by means of Scheimpflug imaging (Pentacam HR). RESULTS: The median age was 46.8 years (range: 10.0-90.3), and involved 827 eyes of 827 patients. Posterior corneal astigmatism was a median of -0.30 diopters (D) and exceeded 0.50 D in 12.56%. The ratio of the anterior-to-posterior corneal radius was a median of 1.217 (range: 1.021-1.402). The correlation between this ratio and age was significant (r = -0.219; P < 0.001). The correlation between anterior and posterior corneal astigmatism and age was significant. At the anterior surface, the ratio of with-the-rule astigmatism was 80.0% for the age range 10 to 20, decreasing to 36.0% for those aged over 81 years, whereas the ratio of against-the-rule astigmatism increased from 7.1% to 44.0%. At the posterior surface, the ratio of with-the-rule astigmatism was 94.3% for the age range 10 to 20 years, decreasing to 84.0% for those aged over 81 years, whereas the ratio of against-the-rule astigmatism increased from 1.4% to 8.0%. CONCLUSIONS: The posterior cornea significantly influences corneal astigmatism. Its power value and orientation are much more stable with advancing age compared with anterior surface values.

Analysis of surgically induced astigmatism on the posterior surface of the cornea.

PURPOSE: To measure surgically induced astigmatism (SIA) on the posterior surface of the cornea using Scheimpflug-based keratometry on eyes with with-the-rule astigmatism. METHODS: Repeated Scheimpflug-based keratometry was obtained preoperatively and a mean of 8.65 weeks postoperatively following superior clear corneal incisions. Differences in the keratometric values and SIA were determined on the anterior and posterior surfaces separately and the data were analyzed. RESULTS: The study included 88 eyes of 88 patients (age range: 46.4 to 87.5 years), with the steepest total corneal meridian between 75° and 105°. Preoperatively, the magnitude of the anterior and posterior corneal astigmatism was 0.74 ± 0.44 and 0.29 ± 0.14 diopters (D), respectively, which was greater than 0.5 D in 10 eyes (11.36%). The difference between preoperative and postoperative keratometric data on the posterior surface was significant, as was the difference between the preoperative and postoperative posterior astigmatism. The mean magnitude of posterior corneal SIA was 0.32 ± 0.29 D, which was 0.5 D or greater in 22 eyes (25.00%). A statistically significant correlation was observed between the diopter of the preoperatively measured posterior corneal astigmatism and the postoperative SIA on the posterior surface (r = 0.34, P = .001). The correlation was not significant between SIA on the anterior and posterior surfaces (r = 0.10, P = .36). CONCLUSIONS: SIA on the posterior surface of the cornea may have a significant role, especially in cases of toric intraocular lens implantation. Posterior corneal astigmatism and SIA may have a significant clinical impact on more precise planning of cataract surgeries.

Examination of ocular biomechanics with a new Scheimpflug technology after corneal refractive surgery.

PURPOSE: To analyze the early results of a new device measuring ocular biomechanics after corneal refractive surgery. PATIENTS AND METHODS: Thirty nine refractive surgery patients were enrolled in the study (age: 32.6±9.9 years). Laser in situ keratomileusis (LASIK) was performed on 52 eyes of 26 patients and photorefractive keratectomy (PRK) was done on 26 eyes of 13 patients. Ten device-specific biomechanical parameters, intraocular pressure (IOP) and pachymetry were measured preoperatively and at day 1, week 1 and month 1 after the surgeries with a new technology based on Scheimpflug imaging (CorVis ST, Oculus). RESULTS: In case of LASIK, the day after the procedure, radius values showed significant differences compared to preoperative data. One month after surgery, radius values, velocity of the second applanation and pachymetry showed significant differences compared to preoperative data. In case of PRK, the day after the procedure, significant differences in IOP, maximum amplitude at the apex, A1 time, A2 velocity and highest concavity time were measured. After 1 month of PRK, there were no differences in the parameters compared to preoperative data except pachymetry. CONCLUSIONS: We observed that some specific biomechanical parameters changed measured with CorVis ST after LASIK and PRK, in the early postoperative time. However, most of these parameters remain unchanged after one month of LASIK and PRK compared to preoperative data.

Scheimpflug imaged corneal changes on anterior and posterior surfaces after collagen cross-linking.

AIM: To compare the anterior and posterior corneal parameters before and after collagen cross-linking therapy for keratoconus. METHODS: Collagen cross-linking was performed in 31 eyes of 31 keratoconus patients (mean age 30.6±8.9y). Prior to treatment and an average 7mo after therapy, Scheimpflug analysis was performed using Pentacam HR. In addition to corneal thickness assessments, corneal radius, elevation, and aberrometric measurements were performed both on anterior and posterior corneal surfaces. Data obtained before and after surgery were statistically analyzed. RESULTS: In terms of horizontal and vertical corneal radius, and central corneal thickness no deviations were observed an average 7mo after operation. Corneal higher order aberration showed no difference neither on anterior nor on posterior corneal surfaces. During follow-up period, no significant deviation was detected regarding elevation values obtained by measurement in mm units between the 3.0-8.0 mm-zones. CONCLUSION: Corneal stabilization could be observed in terms of anterior and posterior corneal surfaces, elevation and higher order aberration values 7mo after collagen cross-linking therapy for keratoconus.

Paired opposite clear corneal incision: time-related changes of its effect and factors on which those changes depend.

PURPOSE: To assess astigmatism induced by paired opposite clear corneal incision (OCCI) compared to single incisions and to investigate factors on which its effect depends. METHODS: The study comprised 326 eyes from 326 patients. In patients with <1.0 D corneal astigmatism, clear corneal incision was performed (CC group, n = 245), and in those with >1.0 D preoperative corneal astigmatism, a second, opposite clear corneal incision was made (OCCI group, n = 81). Both groups consisted of superior, temporal, and oblique subgroups according to the steepest meridian. Prior to the surgery, and after surgery, repeated keratometry was performed and surgically induced astigmatism (SIA) was calculated using vector analysis. RESULTS: Two weeks after the surgery, the SIA was 0.67 ± 0.44 D in the CC group and 1.15 ± 0.65 D in the OCCI group; 9 weeks after the operation, it was 0.61 ± 0.43 D in the CC group and 0.99 ± 0.57 D in the OCCI group (p<0.001). The SIA showed no significant postoperative change in our groups. CONCLUSIONS: Opposite clear corneal incision reliably induces about 1.0 D of corneal astigmatism on the steep meridian in proportion to the rate of preoperative astigmatism. Its magnitude is independent of the location of the incisions and its effect remains unchanged during the postoperative period.

Intraoperative and postoperative corneal thickness change after collagen crosslinking therapy.

PURPOSE: To assess intraoperative and postoperative changes in corneal thickness subsequent to riboflavin-UVA (collagen crosslinking [CXL]) treatment. METHODS: Forty-one eyes of 41 patients (mean age 27.97 ± 6.97 years) were treated with CXL technique. During treatment, isotonic riboflavin was instilled and corneal thickness measurements were obtained at the cornea apex, the thinnest point, and the pupil center at 15 and 30 minutes, then 3 days, 1 week, and 1, 3, 6, and 12 months after surgery using Pentacam HR and an ultrasound pachymeter. RESULTS: A decrease in corneal thickness was detected 15 minutes intraoperatively with a value of 108.95 ± 48.6 µm, and 112.35 ± 47.3 µm at 30 minutes (p<0.001). Three days after the operation, no deviation was found from the initial values (p = 0.17). No further changes were detected during the follow-up period. CONCLUSIONS: Isotonic riboflavin solution used during CXL treatment resulted in a significant decrease in corneal thickness, but its effect had disappeared by postoperative day 3.

Substantial expression of luteinizing hormone-releasing hormone (LHRH) receptor type I in human uveal melanoma.

Uveal melanoma is the most common primary intraocular malignancy in adults, with a very high mortality rate due to frequent liver metastases. Consequently, the therapy of uveal melanoma remains a major clinical challenge and new treatment approaches are needed. For improving diagnosis and designing a rational and effective therapy, it is essential to elucidate molecular characteristics of this malignancy. The aim of this study therefore was to evaluate as a potential therapeutic target the expression of luteinizing hormone-releasing hormone (LHRH) receptor in human uveal melanoma. The expression of LHRH ligand and LHRH receptor transcript forms was studied in 39 human uveal melanoma specimens by RT-PCR using gene specific primers. The binding charachteristics of receptors for LHRH on 10 samples were determined by ligand competition assays. The presence of LHRH receptor protein was further evaluated by immunohistochemistry. The expression of mRNA for type I LHRH receptor was detected in 18 of 39 (46%) of tissue specimens. mRNA for LHRH-I ligand could be detected in 27 of 39 (69%) of the samples. Seven of 10 samples investigated showed high affinity LHRH-I receptors. The specific presence of full length LHRH receptor protein was further confirmed by immunohistochemistry. A high percentage of uveal melanomas express mRNA and protein for type-I LHRH receptors. Our results support the merit of further investigation of LHRH receptors in human ophthalmological tumors. Since diverse analogs of LHRH are in clinical trials or are already used for the treatment of various cancers, theseanalogs could be considered for the LHRH receptor-based treatment of uveal melanoma.

Repeatability of ocular biomechanical data measurements with a Scheimpflug-based noncontact device on normal corneas.

PURPOSE: To analyze the repeatability of a new device measuring ocular biomechanical properties, central corneal thickness (CCT), and intraocular pressure (IOP) and to investigate these parameters and their correlations in healthy eyes. METHODS: Three consecutive measurements were performed on each eye using the CorVis ST device (Oculus Optikgeräte, Inc., Wetzler, Germany). Ten specific parameters, CCT, and IOP were measured. Biometric data were recorded with IOLMaster (Carl Zeiss Meditec, Jena, Germany). RESULTS: This study comprised 75 eyes of 75 healthy volunteers (mean age: 61.24 ± 15.72 years). Mean IOP was 15.02 ± 2.90 mm Hg and mean CCT was 556.33 ± 33.13 µm. Intraclass correlation coefficient (ICC) was 0.865 for IOP and 0.970 for CCT, and coefficient of variation was 0.069 for IOP and 0.008 for CCT. ICC was 0.758 for maximum amplitude at highest concavity and 0.784 for first applanation time, and less than 0.6 for all other parameters. The device-specific data showed no significant relationship with age and axial length. Flattest and steepest keratometric values and IOP showed a significant correlation with the 10 device-specific parameters. CONCLUSIONS: The CorVis ST showed high repeatability for only IOP and pachymetric values. Single measurements are not reliable for the 10 device-specific parameters. The device allows for conducting clinical examinations and screening for surgeries altering ocular biomechanical properties with some form of averaging of multiple measurements.

Accommodation in phakic and pseudophakic eyes measured with subjective and objective methods.

PURPOSE: To measure accommodation subjectively and objectively and assess anterior segment changes during accommodation in phakic eyes and pseudophakic eyes. SETTING: Department of Ophthalmology, Medical Health and Science Centre, University of Debrecen, Debrecen, Hungary. DESIGN: Case series. METHODS: Subjective and objective accommodation measurements and pupillometry were performed in phakic and pseudophakic patients. Refraction and pupil diameter were recorded with different accommodation stimuli. Corneal higher-order aberrations (HOAs) and anterior chamber depths (ACDs) were detected with a rotating Scheimpflug camera. RESULTS: The mean age of the 44 patients in the phakic group was 36.34 years ± 16.6 (SD) and of the 27 patients in the pseudophakic group, 69.3 ± 9.98 years. The mean subjective accommodation was 4.49 ± 3.48 diopters (D) in phakic eyes and showed significant correlation with age, spherical aberration, changes in pupil diameter, and ACD. The mean subjective accommodation was 0.50 ± 0.28 D in pseudophakic eyes. In phakic eyes, the mean objective accommodation was 0.46 ± 1.02 D, 1.06 ± 1.33 D, and 2.2 ± 1.9 D with 2.0 D, 3.0 D, and 5.0 D, respectively, of stimulus. In pseudophakic eyes, measurable objective accommodation was recorded. In phakic eyes, the correlations were significant between these values and age, changes in ACD, pupil size, and corneal spherical aberration. In pseudophakic eyes, the only correlation was with the spherical equivalent value. CONCLUSIONS: The magnitude of accommodation was greater with subjective measures than objective measures. In pseudophakic eyes, senile miosis and HOAs can be regarded as underlying factors in subjective accommodation; however, objective accommodation is not clinically significant. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Two-year safety and efficacy of ranibizumab 0.5 mg in diabetic macular edema: interim analysis of the RESTORE extension study.

OBJECTIVE: To evaluate the 2-year safety and efficacy of ranibizumab 0.5 mg in diabetic macular edema (DME). DESIGN: Twenty-four-month, open-label, multicenter, Phase IIIb extension study. PARTICIPANTS: Two hundred forty of 303 patients with visual impairment due to DME who completed the RESTORE core study and entered the extension. METHODS: All patients were eligible to receive ranibizumab 0.5 mg pro re nata (PRN) from month 12 (end of core study) to month 36 based on best-corrected visual acuity (BCVA) stability and disease progression retreatment criteria. Patients were also eligible to receive laser PRN according to Early Treatment Diabetic Retinopathy Study guidelines. A preplanned interim analysis was performed at month 24, stratifying by treatment groups as in the RESTORE core study and referred to as prior ranibizumab, ranibizumab plus laser, or laser groups in the extension. MAIN OUTCOME MEASURES: Incidence of ocular and nonocular adverse events (AEs) and mean change in BCVA. RESULTS: Two hundred twenty patients (92%) completed the month 24 visit. Over 2 years, the most frequent ocular serious AE (SAE) and AE were cataract (2.1%) and eye pain (14.6%), respectively. The main nonocular AEs were nasopharyngitis (18.8%) and hypertension (10.4%). There were no cases of endophthalmitis, and the incidences of nonocular SAEs were low. Of the patients entering the extension, 4 deaths were reported in the second year, none of which were related to study drug or procedure. Mean BCVA gain, central retinal thickness (CRT) decrease, and National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) composite score observed at month 12 were maintained at month 24 (prior ranibizumab: +7.9 letters, -140.6 µm, and 5.6, respectively; prior ranibizumab plus laser: +6.7 letters, -133.0 µm, and 5.8, respectively), with an average of 3.9 (prior ranibizumab) and 3.5 ranibizumab injections (prior ranibizumab plus laser). In patients treated with laser alone in the core study, the mean BCVA, CRT, and NEI VFQ-25 composite score improved from month 12 to month 24 (+5.4 letters, -126.6 µm, and 4.3, respectively), with an average of 4.1 ranibizumab injections. CONCLUSIONS: Ranibizumab 0.5 mg administered according to prespecified visual stability and disease progression criteria was well tolerated, with no new safety concerns identified over 2 years. Overall, an average of 3.8 ranibizumab injections was sufficient to maintain (prior ranibizumab) or improve (prior laser) BCVA, CRT, and NEI VFQ-25 outcomes through the second year. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Assessment of tear osmolarity and other dry eye parameters in post-LASIK eyes.

PURPOSES: To assess the tear osmolarity using the TearLab device after laser in situ keratomileusis (LASIK) and to compare the values with those obtained by traditional tear film tests before and after the procedure. METHODS: Thirty eyes of 15 refractive surgery candidates (5 men and 10 women of mean age: 30.55 ± 11.79 years) were examined. Using a special questionnaire (Ocular Surface Disease Index), subjective dry eye complaints were evaluated, and then, the tear osmolarity was measured with the TearLab system (TearLab Corporation) and conventional dry eye tests were carried out. Examinations were performed preoperatively and at 1, 30, and 60 days after the surgery. RESULTS: The mean value of tear osmolarity was 303.62 ± 12.29 mOsm/L before the surgery and 303.58 ± 20.14 mOsm/L at 60 days after the treatment (P = 0.69). Mean lid parallel conjunctival folds value was 0.68 ± 0.68 before the procedure and 0.58 ± 0.65 subsequent to surgery (P = 0.25). Meibomian gland dysfunction was not detected. No significant deviation was observed in the values of Schirmer test, corneal staining, tear break-up time, and lid parallel conjunctival folds when compared with postoperatively obtained values during the follow-up period (P > 0.05). CONCLUSIONS: During LASIK flap creation, intact corneal innervation is damaged, and the ocular surface lacrimal functional unit can be impaired. In our study, no abnormal dry eye test results were observed before or after the procedure. Based on our results, LASIK treatment is safe for dry eye involving the administration of adequate artificial tears for a minimum of 3 months.