Successful treatment of Fusarium solani anterior chamber involvement secondary to contact lens associated corneal ulcer with intracameral Amphotericin B.

Background: Fusarium spp. are leading fungal pathogenes in contact lens associated keratitis and may evoke endophthalmitis. Since Fusarium spp. are highly resistant to antifungal drugs, globe integrity is threatened. Case: A woman developed fungal anterior chamber involvement after contact lens associated corneal ulcer formation. She presented with a painful eye with hypopyon and a mass presumably of fungal origin growing on the iris and anterior lens capsule. A biopsy confirmed Fusarium solani. Only multiple lavages of the anterior segment with Amphotericin B achieved convalescence. Conclusion: In the initial stage of contact lens associated keratitis, it is often hard to differentiate between etiology. However, keratitis which are treatment resistant to antibacterials are suspicious for fungal origin. For proper treatment, identification of pathogen is crucial. Due to poor tissue penetration of the lipophilic anti-fungal agents and slow fungal replication rate, multiple lavages of the anterior chamber are often required to handle fungal infections.

[Evaluation of Ophthalmic Follow-up Care of Former Pre-term and Full-term Infants Aged from 4 to 10 Years in Germany - Results of the Wiesbaden Prematurity Study (WPS)]. / 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 full-term 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) ≤ 32 weeks and 264 former full-term born infants (FT) with a 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-term infants 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: A Randomized Clinical Trial.

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. Trial Registration: clinicaltrials.gov Identifier: NCT02134457 and clinicaltrialsregister.eu Identifier: 2013-002539-13.

EFFECT OF PATIENTS' CLINICAL INFORMATION ON THE DIAGNOSIS OF AND DECISION TO TREAT RETINOPATHY OF PREMATURITY.

PURPOSE: To evaluate the effect of patients' clinical information on experts' diagnoses of retinopathy of prematurity (ROP) and decisions to treat. METHODS: Seven experts assessed wide-field fundus photographs of eyes of 52 premature infants of ≤30 weeks' gestational age or ≤1,500 g birthweight (BW) for ROP diagnosis (stage, plus disease, and aggressive posterior ROP) and the necessity for treatment for 2 days. On Day 1, they were masked to all patient data. On Day 2, they were given information on gestational age and BW. RESULTS: A significant shift in the experts' ratings toward a less aggressive ROP grading stage (P = 0.006) and less frequent decision for intervention (P = 0.021) was observed after receipt of patients' clinical information. This was truer for heavier/less premature infants (gestational age ≥ 28 0/7 weeks or BW ≥ 900 g) than those with very low BWs/high prematurity (gestational age < 24 0/7 weeks or BW < 600 g) (ROP stage P = 0.009 vs. P = 0.399, treatment decision P = 0.022 vs. P = 0.648). CONCLUSION: These results suggest knowledge of patients' clinical information influences the grading of ROP disease and decision for treatment. Retinopathy of prematurity staging seemed to be set at a lower level and the decision for treatment at a higher threshold for heavier/less premature babies. Our findings may have implications for further refinements in ROP assessment.

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 ≤32 weeks and 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 ≤7 years for spherical equivalent, astigmatism, corneal diameter, and axial length. In preterm infants 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.

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.

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.

Inter-expert and intra-expert agreement on the diagnosis and treatment of retinopathy of prematurity.

PURPOSE: To evaluate inter-expert and intra-expert agreement on the diagnosis and treatment of retinopathy of prematurity (ROP). DESIGN: Prospective intra- and inter-rater reliability analysis. METHODS: In this multicenter study, 260 wide-field digital photographs of 52 patients were presented to 7 recognized ROP experts on 2 consecutive assessment days 8 weeks apart. Experts were asked to assess the patients for ROP stage, presence of plus disease, presence of aggressive posterior ROP, necessity for treatment, and suggested treatment. Agreement levels were measured with Fleiss' kappa and Cohen's kappa. RESULTS: Inter-expert agreement was fair for the ROP stage (κ = 0.24), plus disease (κ = 0.32), and aggressive posterior ROP (κ = 0.35); moderate for the necessity for treatment (κ = 0.41); and fair for the kind of treatment (κ = 0.38). Perfect inter-expert agreement was found in 9.6% of all patients for ROP stage 0-5, 45.1% for ≥ stage 2 ROP, 17.3% for plus disease, 57.7% for aggressive posterior ROP, and 25% for the necessity for treatment. Intra-expert agreement was higher than inter-expert agreement and was moderate for the ROP stage (κ = 0.56) and plus disease (κ = 0.51), moderate to substantial for aggressive posterior ROP (κ = 0.60), moderate for the necessity for treatment (κ = 0.47), and substantial for the kind of treatment (κ = 0.63). CONCLUSIONS: ROP diagnosis and treatment decisions differ between experts and by 1 expert made on different days, indicating that the grading process is subjective and there is an observer bias when diagnosing ROP. These results could influence current practice in ROP assessment and training, and prompt further refinement of international ROP guidelines.

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.

Diurnal Intraocular Pressure Profiles in Chronic Open-Angle Glaucoma.

PURPOSE: To evaluate day-and-night intraocular pressure (IOP) profiles in normal and glaucomatous eyes. DESIGN: Hospital-based clinical observational study. METHODS: The study included 3561 day-and-night profiles of IOP measurements performed by Goldmann applanation tonometry on 1408 eyes of 720 normal Caucasian subjects or chronic open-angle glaucoma patients. RESULTS: For all groups except the secondary open-angle glaucoma group, IOP was highest at 7 a.m., followed by noon and 5 p.m., and finally at 9 p.m. or midnight. In secondary open-angle glaucoma, mean measurements did not vary significantly during day and night. The profile amplitude (mean: 5.5 2.8 mm Hg) was significantly (P < 0.001) higher in the secondary open-angle glaucoma group than in the normal-pressure glaucoma group and the normal group. The two latter groups did not vary significantly (P = 0.47) in profile amplitude. Expressed as percentage of the mean IOP, the IOP amplitude did not vary significantly between any of the study groups. The inter-eye IOP difference for any measurement time was significantly (P < 0.001) smaller than the IOP profile amplitude. CONCLUSIONS: Treated secondary open-angle glaucoma eyes did not exhibit the normal day-and-night pressure profile which was usually shown in normal eyes and eyes treated for other types of chronic open-angle glaucoma. The day-and-night IOP amplitude in absolute terms is highest in secondary open-angle glaucoma. In relative terms, the IOP amplitude did not vary significantly between the various types of chronic open-angle glaucoma. Inter-eye IOP differences were significantly (P < 0.001) smaller than the IOP profile amplitude.

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.

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.

Evolution of central corneal thickness in children with congenital glaucoma requiring glaucoma surgery.

BACKGROUND: The purpose of the study was to investigate the evolution of central corneal thickness (CCT) in correlation to the intraocular pressure (IOP) in children with congenital glaucoma before and after glaucoma surgery. METHODS: Nine eyes of five children (age 2 weeks to 6 months, mean 23 weeks) underwent trabeculotomy for congenital glaucoma. Corneal ultrasound pachymetry (PacScan 3000 AP, Technomed, Germany), tonometry using the Perkins tonometer, and slit-lamp examination (additionally to a clinical routine examination with retinoscopy, funduscopy, measurement of axial length and corneal diameter) were performed before and for at least 12 months after glaucoma surgery. In all children, corneal pachymetry and slit-lamp biomicroscopy--and whenever possible applanation tonometry--were performed without sedation or general anesthesia. If measurement of the IOP was not possible otherwise (in four of the five children), sedation with midazolam orally was used to measure the IOP at 2 weeks, 6 weeks, and 3 months after trabeculotomy, then every 3 months. RESULTS: Six of nine eyes had biomicroscopically clear corneas without visible corneal edema before trabeculotomy. In three eyes, a corneal edema was visible in at least one quadrant of the cornea. Regarding all eyes together, mean CCT was 651 +/- 138 microm before trabeculotomy; this decreased to 592 +/- 119 microm within 2 weeks after trabeculotomy. At 6 weeks and 3 months there was a further regression to 569.4 +/- 16 microm. Mean IOP was 18.6 +/- 7.5 mmHg before and decreased to 14.8 +/- 5.8 mmHg after glaucoma surgery. Regarding IOP data obtained under general anaesthesia, decrease of CCT was significantly correlated with decrease in IOP. There was no significant difference in the correlation between eyes with and without visible corneal edema. CONCLUSIONS: Corneal ultrasound pachymetry appears to be a valuable additional measure in the follow-up of infants and small children requiring glaucoma surgery.

Iris colour, optic disc dimensions, degree and progression of glaucomatous optic nerve damage.

PURPOSE: To evaluate whether iris colour influences size and shape of the optic nerve head and risk for glaucoma progression. METHODS: The hospital-based observational study included 1973 eyes of 1012 Caucasian subjects with ocular hypertension or chronic open-angle glaucoma. For all patients, colour stereo optic disc photographs were evaluated, and corneal pachymetry and achromatic perimetry were performed. Main outcome measures were optic nerve head parameters, the development or progression of visual field defects and iris colour. RESULTS: In most of the study groups, size of the optic disc, neuroretinal rim, alpha zone and beta zone of parapapillary atrophy, retinal vessel diameter and central corneal thickness did not differ significantly between eyes with blue, green, brown and mixed iris colour. In the normal-pressure glaucoma group, neuroretinal rim area was smallest in the population with mixed-coloured eyes and largest in the group of eyes with brown irides (P = 0.001 after correction for inter-eye dependency and multiple testing). For the ocular hypertensive subjects and glaucoma patients with follow-up examinations, the rate of development or progression of glaucomatous visual field loss was not significantly associated with iris colour (P = 0.060). CONCLUSIONS: In Caucasian subjects, iris colour does not have a major association with the size of the optic nerve head structures, central corneal thickness and retinal arterial diameter. In Caucasian patients with ocular hypertension or chronic open-angle glaucoma, an influence of iris colour on the risk for development or progression of glaucomatous visual field defects could not be confirmed.

Central corneal thickness and development of glaucomatous optic disk hemorrhages.

PURPOSE: To evaluate whether central corneal thickness influences the development of optic disk hemorrhages in chronic open-angle glaucoma. DESIGN: Prospective observational clinical study. METHODS: The study included 390 eyes of 223 white subjects with chronic open-angle glaucoma observed during a mean follow-up time of 61.3 +/- 36.4 months. Central corneal thickness was measured by corneal pachymetry. RESULTS: The event of optic disk hemorrhages during follow-up was detected in 63 eyes (16.2%). Development of optic disk hemorrhages was, univariately (P = .73) as well as in a multiple Cox regression analysis, controlling for age, sex, normal tension glaucoma, intraocular pressure, neuroretinal rim area, and size of beta zone of peripapillary atrophy, statistically independent (P = .56) of central corneal thickness. CONCLUSIONS: Development of optic disk hemorrhages may not be markedly influenced by central corneal thickness.

Single intraocular pressure measurements and diurnal intraocular pressure profiles.

PURPOSE: To evaluate the probability of a single intraocular pressure measurement to be the highest measurement within a diurnal intraocular pressure profile. DESIGN: Hospital-based clinical, observational study. METHODS: The study included 3,025 day-and-night intraocular pressure profiles measured on 1,072 eyes of 547 Caucasian glaucoma patients or glaucoma suspects. Applanation tonometry was performed at 7 am, noon, 5 pm, 9 pm, and midnight. RESULTS: Intraocular pressure measurements were highest at 7 am, noon, 5 pm, 9 pm, and midnight, respectively, in 20.4%, 17.8%, 21.3% 13.9%, and 26.7% of the profiles, respectively. The measurement taken at 7 am was significantly (P < .001) closest to the maximal value of the profile. CONCLUSIONS: Any single intraocular pressure measurement taken between 7 am and 9 pm has a higher than 75% chance to miss the highest point of a diurnal curve. Intraocular pressure may be measured at different times of the day to have the best chance of observing the maximal value.

Bilateral optic neuropathy and unilateral tonic pupil associated with acute human herpesvirus 6 infection: a case report.

BACKGROUND: Human herpesvirus 6 (HHV-6), a widespread virus and causative agent of exanthema subitum in children, has been associated with a number of neurologic disorders including cranial nerve palsies, seizures, encephalitis, meningitis, and multiple sclerosis. PATIENT: A 31-year-old man presented with bilateral optic neuropathy, disc edema, and unilateral tonic pupil, which were found to be associated with acute HHV-6 infection. The patient had been suffering from juvenile diabetes for 5 years. One week after onset of intravenous antiviral therapy with foscarnet, disc edema subsided, and tonic pupil reaction was no longer detectable. CONCLUSIONS: HHV-6 infection may play a role as a causative agent in patients with optic neuropathy and tonic pupil.