Circadian Intraocular Pressure Profiles in Chronic Open Angle Glaucomas

Purpose: To evaluate circadian intraocular pressure (IOP) profiles in eyes with different types of chronic open-angle glaucoma (COAG) and normal eyes. Methods: This study included 3,561 circadian IOP profiles obtained from 1,408 eyes of 720 Caucasian individuals including glaucoma patients under topical treatment (1,072 eyes) and normal subjects (336 eyes). IOP profiles were obtained by Goldmann applanation tonometry and included measurements at 7 am, noon, 5 pm, 9 pm, and midnight. Results: Fluctuations of circadian IOP in the secondary open-angle glaucoma (SOAG) group (6.96±3.69 mmHg) was significantly (P<0.001) higher than that of the normal pressure glaucoma group (4.89±1.99 mmHg) and normal eyes (4.69±1.95 mmHg); but the difference between the two latter groups was not significant (P=0.47). Expressed as percentages, IOP fluctuations did not vary significantly among any of the study groups. Inter-ocular IOP difference for any measurement was significantly (P<0.001) smaller than the profile fluctuations. In all study groups except the SOAG group, IOP was highest at 7 am, followed by noon, 5 pm, and finally 9 pm or midnight. In the SOAG group, mean IOP measurements did not vary significantly during day and night. Conclusions: In contrast to normal eyes and eyes with primary open-angle glaucoma under topical antiglaucoma treatment, eyes with SOAG under topical treatment do not show the usual circadian IOP profile in which the highest IOP values occur in the morning, and the lowest in the evening or at midnight. These findings may have implications for timing of tonometry. Fluctuation of circadian IOP was highest in SOAG compared to other types of open angle glaucomas

The effects of midazolam on intraocular pressure in children during examination under sedation

Background: To obtain reliable and accurate measurements of the intraocular pressure (IOP) in children often requires sedation or anaesthesia. Therefore, we investigated the effects of oral midazolam on IOP in children. Methods: In a prospective study, IOP was measured in 72 eyes of 36 cooperative children without glaucoma requiring general anaesthesia (mean age 3.5±1.3 years, body weight ≤20 kg) by using a Perkins hand-held tonometer. Measurements of IOP were performed before, and 15 and 30 min after sedation with orally administered midazolam (1 mg/kg) given as preoperative medication, and 5 and 15 min after induction of general anaesthesia. The individual IOP courses were analysed. Results: In all of the cooperative children, IOP measurement was possible after sedation with midazolam. Mean IOP was 11.2±0.3 mmHg before sedation, 10.9±0.2 mmHg at 15 min, and 10.7±0.3 mmHg 30 min after administration of midazolam. This small decrease was not statistically significant, whilst the IOP decline at 5 and 15 min after induction of general anaesthesia was statistically significant (p<0.0001). Conclusion: Sedation with midazolam can be assumed to be an applicable, well-tolerated, safe method for IOP measurements in children

Phase 3, Randomized, 20-Month Study of the Efficacy and Safety of Bimatoprost Implant in Patients with Open-Angle Glaucoma and Ocular Hypertension (ARTEMIS 2)

Objective- To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10 and 15 µg bimatoprost implant in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods- This randomized, 20-month, multicenter, masked, parallel-group, phase 3 trial enrolled 528 patients with OAG or OHT and an open iridocorneal angle inferiorly in the study eye. Study eyes were administered 10 or 15 µg bimatoprost implant on day 1, week 16, and week 32, or twice-daily topical timolol maleate 0.5%. Primary endpoints were IOP and IOP change from baseline through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD). Results- Both 10 and 15 µg bimatoprost implant met the primary endpoint of noninferiority to timolol in IOP lowering through 12 weeks. Mean IOP reductions from baseline ranged from 6.2–7.4, 6.5–7.8, and 6.1–6.7 mmHg through week 12 in the 10 µg implant, 15 µg implant, and timolol groups, respectively. IOP lowering was similar after the second and third implant administrations. Probabilities of requiring no IOP-lowering treatment for 1 year after the third administration were 77.5% (10 µg implant) and 79.0% (15 µg implant). The most common TEAE was conjunctival hyperemia, typically temporally associated with the administration procedure. Corneal TEAEs of interest (primarily corneal endothelial cell loss, corneal edema, and corneal touch) were more frequent with the 15 than the 10 µg implant and generally were reported after repeated administrations. Loss in mean CECD from baseline to month 20 was ~ 5% in 10 µg implant-treated eyes and ~ 1% in topical timolol-treated eyes. Visual field progression (change in the mean deviation from baseline) was reduced in the 10 µg implant group compared with the timolol group. Conclusions- The results corroborated the previous phase 3 study of the bimatoprost implant. The bimatoprost implant met the primary endpoint and effectively lowered IOP. The majority of patients required no additional treatment for 12 months after the third administration. The benefit-risk assessment favored the 10 over the 15 µg implant. Studies evaluating other administration regimens with reduced risk of corneal events are ongoing. The bimatoprost implant has the potential to improve adherence and reduce treatment burden in glaucoma

Etiology and Treatment of Choroidal Neovascularization in Pediatric Patients

Purpose: To assess the etiology, clinical features, and outcome of choroidal neovascularization (CNV) in children. Methods: We retrospectively assessed 10 eyes of 8 patients younger than 18 years diagnosed with CNV. The main clinical parameters included predisposing ocular pathologies, best-corrected visual acuity before and after treatment, characteristics of CNV, and treatment modalities. Results: Two boys and 6 girls with CNV and a mean age of 13.9 years (SD 1.9, range 11-16 years) were included. Two patients developed bilateral CNV within the follow-up time. The development of CNV was secondary to the following pathologies: choroidal osteoma (n = 3), pathologic myopia (n = 1), punctate inner choroidopathy (n = 1), hereditary macular dystrophy (n = 2), and angioid streaks (n = 1). Idiopathic CNV was diagnosed in 2 children without any obvious associated ocular pathology. In 9 eyes, CNV was treated by intravitreal anti-vascular endothelial growth factor (VEGF) administration (n = 6), photodynamic therapy (n = 1), or combination therapy (n = 3). One eye remained untreated because of advanced disease. Conclusions: Pediatric CNV is a rare but sight-threatening retinal disease. So far, no standard treatment has been validated. Since the establishment of intravitreal anti-VEGF therapy, laser coagulation and photodynamic therapy have lost their significance as therapy for CNV

Clinical Features and Outcome of Paediatric Retinal Detachment

Purpose: The aim of this study was to assess the clinical features and outcome of paediatric retinal detachment (RD). Methods: Ninety-five eyes of 87 children under 18 years of age with RD were assessed. The risk factors, morphology of RD, therapeutic approach and functional results were evaluated. Results: Sixty-seven boys and 20 girls with a mean age of 10.4 years (standard deviation 5.5) presented with RD. The following risk factors were identified: myopia (23%), congenital or developmental ocular abnormalities (37%), history of ocular trauma (40%) and previous ocular surgery (27%). Seventy-seven (81%) eyes underwent surgery. The primary reattachment rate was 44%. In 18%, reattachment was achieved after several surgeries. The overall recurrence rate after surgical reattachment was 39%. Conclusions: Paediatric RD is a sight-threatening condition. Often, aggravating factors, such as delayed diagnosis, hereditary ocular abnormalities or strong vitreous adherence, are present. Hopefully, modern surgical techniques may contribute to a better outcome of RD in the future. (C) 2017 S. Karger AG, Base

Optic disc morphology in premature infants

Background: To date, little is known about the morphology of optic discs in premature infants. However, optic disc morphology and optic nerve development are two factors that potentially influence visual function in infants. Thus we analysed the morphology of the optic disc and its correlation with gestational age and birth weight. Methods: In a retrospective trial, we assessed the widefield images (RetCam system) of 111 optic discs of 61 premature infants. We evaluated the form of the optic disc, defined by the ratio of the vertical to the horizontal diameter, the presence or absence of visible disc cupping, the cup to disc ratio and the presence or absence of a double ring (a concentric paler zone around the optic disc). Results: 110 of 111 optic discs had a vertical–oval form. We found a significant negative correlation between the form of the optic disc and birth weight (p=0.003) and gestational age (p=0.03); 75% of optic discs showed a double ring and 89% had visible disc cupping. Conclusions: In our study, premature birth was associated with the presence of a double ring. A low birth weight and low gestational age influence the form of the optic disc

Axial Length and Anterior Segment Alterations in Former Preterm Infants and Full-Term Neonates Analyzed With Scheimpflug Imaging

Purpose: To compare the axial length and anterior segment alterations in preterm infants with and without retinopathy of prematurity with those of full-term infants. Methods: The Wiesbaden Prematurity Study investigated 503 participants of former gestational age = 37 weeks now being aged 4 to 10 years. This study included 485 participants in the prospective controlled cross-sectional, hospital-based study with successful Pentacam Scheimpflug imaging. Anterior segment parameters, axial length measurements, and associated factors were analyzed. Results: Corneal thickness did not differ between former preterm and full-term infants. Significant differences were found between preterm and full-term infants now aged = 8 years compared with full terms of the same age, we found a significant difference only in the corneal diameter. In multivariable analysis of the corneal diameter, we detected an association with birth weight and perinatal adverse events. Astigmatism correlated with birth weight and laser treatment, anterior chamber depth with birth weight, laser treatment and age at examination, and axial length with birth weight and age at examination. Conclusions: This study demonstrated altered axial length and anterior segment morphology in former preterm infants, especially in the first years of life. In addition, we observed that preterm infants seemed to catch up, so that the differences in ocular growth in terms of spherical equivalent, astigmatism, and axial length decreased within the first 8 years of life

Evaluation der augenärztlichen Versorgung ehemaliger früh- und reifgeborener Kinder im Alter von 4 bis 10 Jahren in Deutschland – Ergebnisse der Wiesbaden Prematurity Study (WPS)

Background The purpose of this investigation was to analyse the ophthalmic follow-up care of former pre-term and fullterm born infants aged 4 to 10 years in the clinical practice and the comparison to the recommendations of the national ophthalmic guidelines. Methods For the prospective Wiesbaden Prematurity Study (WPS), 503 infants were examined: 239 former pre-term infants (PT) with gestational age (GA) = 37 weeks aged 4 to 10 years. Ophthalmic examination was performed including refractive measurements and orthoptic examination. Anisometropia was defined as a difference of >= 1 D spherical equivalent. Data was assessed if an ophthalmological examination was performed after hospital discharge, and how many times the ophthalmologist was contacted within the last 12 months. Results Overall, strabismus and anisometropia were present in 18 and 10% of all PT, and in 2 and 5% of all FT infants, respectively. In infants aged 4 to 6 years, 65% of all former PT and 42% of all former FT had ophthalmological contacts within the last year ( p = 0.002). 15% of the pre-term infants with strabismus did not have an ophthalmological examination within the last year. The parents of three former pre-term infants reported that they never had an ophthalmologic examination after hospital discharge. Conclusion Two-thirds of the former pre-terminfants participated in a screening examination at the age of 4 to 6 years in the last year according to their parents, which is recommended by the guidelines for the care of former pre-term infants. There is still room for improvement to provide best ophthalmological care for this vulnerable population that have high risk for strabismus and amblyopia

Comparing Alternative Ranibizumab Dosages for Safety and Efficacy in Retinopathy of Prematurity

IMPORTANCE: Anti-vascular endothelial growth factor (VEGF) therapies are a novel treatment option in retinopathy of prematurity (ROP). Data on dosing, efficacy, and safety are insufficient. OBJECTIVE: To investigate lower doses of anti-VEGF therapy with ranibizumab, a substance with a significantly shorter systemic half-life than the standard treatment, bevacizumab. DESIGN, SETTING, AND PARTICIPANTS: This randomized, multicenter, double-blind, investigator-initiated trial at 9 academic medical centers in Germany compared ranibizumab doses of 0.12 mg vs 0.20 mg in infants with bilateral aggressive posterior ROP; ROP stage 1 with plus disease, 2 with plus disease, or 3 with or without plus disease in zone I; or ROP stage 3 with plus disease in posterior zone II. Patients were recruited between September 2014 and August 2016. Twenty infants were screened and 19 were randomized. INTERVENTIONS: All infants received 1 baseline ranibizumab injection per eye. Reinjections were allowed in case of ROP recurrence after at least 28 days. MAIN OUTCOMES AND MEASURES: The primary end point was the number of infants who did not require rescue therapy at 24 weeks. Key secondary end points included time-to-event analyses, progression of physiologic vascularization, and plasma VEGF levels. Stages of ROP were photodocumented and reviewed by an expert committee. RESULTS: Nineteen infants with ROP were enrolled (9 [47.4%] female; median [range] postmenstrual age at first treatment, 36.4 [34.7-39.7] weeks), 3 of whom died during the study (1 in the 0.12-mg group and 2 in the 0.20-mg group). Of the surviving infants, 8 (88.9%) (17 eyes [94.4%]) in the 0.12-mg group and 6 (85.7%) (13 eyes [92.9%]) in the 0.20-mg group did not require rescue therapy. Both ranibizumab doses were equally successful in controlling acute ROP (Cochran-Mantel-Haenszel analysis; odds ratio, 1.88; 95% CI, 0.26-13.49; P = .53). Physiologic intraretinal vascularization was superior in the 0.12-mg group. The VEGF plasma levels were not systematically altered in either group. CONCLUSIONS AND RELEVANCE: This pilot study demonstrates that ranibizumab is effective in controlling acute ROP and that 24% of the standard adult dose (0.12 mg) appears equally effective as 40% (0.20 mg). Superior vascularization of the peripheral retina with 0.12 mg of ranibizumab indicates that the lower dose may be favorable. Unchanged plasma VEGF levels point toward a limited systemic drug exposure after ranibizumab