Increasing pharmacy productivity and reducing medication turnaround times in an Italian comprehensive cancer center by implementing robotic chemotherapy drugs compounding.

INTRODUCTION: The management of antineoplastic drugs used for chemotherapy is widely recognized as a high-risk activity. In 2018, our oncology pharmacy implemented workflow improvements to manage the growing workload due to the centralisation of activities from a hospital's satellite pharmacy, moving towards automated compounding of antineoplastic drugs.The aim of this study was to determine the impact of the centralization on the productivity of the pharmacy department and evaluate the performances of the robotic chemotherapy drugs compounding. MATERIAL AND METHODS: Data were collected from the hospital information system and the workflow management software, and examined over a 3-year period (2017-2019). The total annual throughput in terms of doses prepared and patients treated and the Medication Turnaround Time (MTAT) were determined. Productivity and dosage accuracy were calculated for the robotic system. RESULTS: In 2018, the number of patients treated increased by 16.6%, consequently, the overall number of intravenous preparations compounded in the pharmacy increased by 17.2%. Regarding manual compounding, the total number of antineoplastic preparations decreased by about 2%. Investigational treatments manually compounded increased by about 27%, in contrast to the non-investigational treatments, which decreased by 9.4%. Regarding robotic compounding, the annual production increased by 50.4%. In 2018, the MTAT decreased about 24%. The dosage accuracy and precision of the total amount of doses were -1.1% and 1.2%, respectively. CONCLUSION: This study indicates that in the effort to satisfy an ever-increasing workload, computerization and automation are essential instruments to maintain and ensuring high standards of quality.

Efficacy of four cleaning solutions for the decontamination of selected cytotoxic drugs on the different surfaces of an automated compounding system.

The automated aseptic preparation of ready-to-administer antineoplastic drug solutions with robotic systems reduces the risk of occupational exposure. However, the surfaces in the preparation area of the robot are to be cleaned by wiping with an appropriate cleaning solution. The aim of the study was to evaluate the cleaning efficacy of four cleaning solutions on four surface materials installed in the APOTECAchemo robot. Predefined amounts of cisplatin (Cis), 5-fluorouracil (5-FU), and cyclophosphamide (CP) were intentionally spread on test plates made of stainless steel, aluminium, polyoxymethylene, and polycarbonate just as installed in the robotic system APOTECAchemo. After drying, the plates were cleaned with 0.2% ethanolic NaOH, 0.23% isopropanolic sodium dodecylsulfate (SDS-2P), 0.5% sodium hypochlorite (NaOCl), and 0.1% benzalkonium chloride (BZK) solutions following a standardized wiping protocol. Residual contamination was recovered with wipe tests, Pt was quantified by voltammetry, and 5-FU and CP was quantified by gas chromatography-tandem mass spectrometry (GC-MSMS). The mean residual contamination after cleaning and the cleaning efficacy (CE) rates were calculated and aggregated on different levels. The CE rates varied between 81.5% and 100% and lay in the majority of cases above 90%. The lowest CE rates were registered for Pt contamination. Especially on aluminium surfaces the residual contamination was high. The overall CE rates of the three different drugs and four different surface types amounted to 98.3% for NaOCl, 97.9% for SDS-2P, 96.9% for ethanolic NaOH, and 96.5% for BZK. The tested cleaning solutions proved to be higher than 90% in most cases, but none of them was able to eliminate 100% of the intentional surface contamination of three antineoplastic drugs on the test plates. The cleaning efficacy varied according to the different surface types and antineoplastic drug. Results could be used in the daily clinical practice to develop and implement effective cleaning procedures.

Early impairment of the full-field photopic negative response in patients with Stargardt disease and pathogenic variants of the ABCA4 gene.

BACKGROUND: To study the photopic negative response of the full-field photopic electroretinography (ERG) in Stargardt patients with pathogenic variants in the ABCA4 gene. METHODS: A retrospective analysis of 35 Stargardt patients with ABCA4 gene pathogenic variants, compared to normal age-matched controls. Patients were clinically followed at the Ophthalmology Department of Fondazione Policlinico Universitario A. Gemelli/Università Cattolica del Sacro Cuore, Rome, Italy. RESULTS: The photopic negative response of the full-field photopic ERG was compromised in most Stargardt patients. In the presence of a normal B-wave, the amplitude ratio between the photopic negative response and the B-wave displayed a 97% accuracy in detecting diseased eyes (receiver operating characteristic curves). CONCLUSIONS: In Stargardt patients with ABCA4 pathogenic mutations, the photopic negative response of the full-field photopic ERG is a very sensitive disease read-out. Its inclusion in standard ERG analysis would be a no-cost addition of practical consequence in the follow-up of Stargardt disease. The early impairment of the photopic negative response suggests that inner retinal function might be affected in Stargardt disease earlier than previously acknowledged.

Nerve growth factor improves visual loss in childhood optic gliomas: a randomized, double-blind, phase II clinical trial.

Paediatric optic pathway gliomas are low-grade brain tumours characterized by slow progression and invalidating visual loss. Presently there is no strategy to prevent visual loss in this kind of tumour. This study evaluated the effects of nerve growth factor administration in protecting visual function in patients with optic pathway glioma-related visual impairment. A prospective randomized double-blind phase II clinical trial was conducted in 18 optic pathway glioma patients, aged from 2 to 23 years, with stable disease and severe visual loss. Ten patients were randomly assigned to receive a single 10-day course of 0.5 mg murine nerve growth factor as eye drops, while eight patients received placebo. All patients were evaluated before and after treatment, testing visual acuity, visual field, visual-evoked potentials, optic coherence tomography, electroretinographic photopic negative response, and magnetic resonance imaging. Post-treatment evaluations were repeated at 15, 30, 90, and 180 days Brain magnetic resonance imaging was performed at baseline and at 180 days. Treatment with nerve growth factor led to statistically significant improvements in objective electrophysiological parameters (electroretinographic photopic negative response amplitude at 180 days and visual-evoked potentials at 30 days), which were not observed in placebo-treated patients. Furthermore, in patients in whom visual fields could still be measured, visual field worsening was only observed in placebo-treated cases, while three of four nerve growth factor-treated subjects showed significant visual field enlargement. This corresponded to improved visually guided behaviour, as reported by the patients and/or the caregivers. There was no evidence of side effects related to nerve growth factor treatment. Nerve growth factor eye drop administration appears a safe, easy and effective strategy for the treatment of visual loss associated with optic pathway gliomas.

Media-fill simulation tests in manual and robotic aseptic preparation of injection solutions in syringes.

OBJECTIVE: The purpose of this study was to evaluate the contamination rate of media-fill products either prepared automated with a robotic system (APOTECAchemo™) or prepared manually at cytotoxic workbenches in the same cleanroom environment and by experienced operators. Media fills were completed by microbiological environmental control in the critical zones and used to validate the cleaning and disinfection procedures of the robotic system. METHODS: The aseptic preparation of patient individual ready-to-use injection solutions was simulated by using double concentrated tryptic soy broth as growth medium, water for injection and plastic syringes as primary packaging materials. Media fills were either prepared automated (500 units) in the robot or manually (500 units) in cytotoxic workbenches in the same cleanroom over a period of 18 working days. The test solutions were incubated at room temperature (22℃) over 4 weeks. Products were visually inspected for turbidity after a 2-week and 4-week period. Following incubation, growth promotion tests were performed with Staphylococcus epidermidis. During the media-fill procedures, passive air monitoring was performed with settle plates and surface monitoring with contact plates on predefined locations as well as fingerprints. The plates got incubated for 5-7 days at room temperature, followed by 2-3 days at 30-35℃ and the colony forming units (cfu) counted after both periods. The robot was cleaned and disinfected according to the established standard operating procedure on two working days prior to the media-fill session, while on six other working days only six critical components were sanitized at the end of the media-fill sessions. Every day UV irradiation was operated for 4 h after finishing work. RESULTS: None of the 1000 media-fill products prepared in the two different settings showed turbidity after the incubation period thereby indicating no contamination with microorganisms. All products remained uniform, clear, and light-amber solutions. In addition, the reliability of the nutrient medium and the process was demonstrated by positive growth promotion tests with S. epidermidis. During automated preparation the recommended limits < 1 cfu per settle/contact plate set for cleanroom Grade A zones were not succeeded in the carousel and working area, but in the loading area of the robot. During manual preparation, the number of cfus detected on settle/contact plates inside the workbenches lay far below the limits. The number of cfus detected on fingertips succeeded several times the limit during manual preparation but not during automated preparation. There was no difference in the microbial contamination rate depending on the extent of cleaning and disinfection of the robot. CONCLUSION: Extensive media-fill tests simulating manual and automated preparation of ready-to-use cytotoxic injection solutions revealed the same level of sterility for both procedures. The results of supplemental environmental controls confirmed that the aseptic procedures are well controlled. As there was no difference in the microbial contamination rates of the media preparations depending on the extent of cleaning and disinfection of the robot, the results were used to adapt the respective standard operating procedures.

Efficacy of UV and UV-LEDs Irradiation Models for Microbial Inactivation Applicable to Automated Sterile Drug Compounding.

LEDs development has attracted attention over conventional mercury lamps for the tiny size, high efficiency, long lifetime, low operating temperature. The antimicrobial effectiveness of traditional UV-lamps radiation (wavelength of 254 nm) compared to UV-C LEDs (LED1 wavelength range 275-286 nm and LED2 range 260-270 nm) was carried out, for possible applications to automated sterile drug compounding. The UV lamp and the tested UV-LED devices remarkably reduced microbial load, following a time-dose response, but the best performance was evidenced by LED1, which guaranteed the complete inactivation of high concentrations of bacteria, yeasts, and spores at doses between 200 and 2000 J/m2.

Spectral-domain optical coherence tomography in Irvine-Gass syndrome.

PURPOSE: To report longitudinal evaluation of morphology and function, by spectral-domain optical coherence tomography and Early Treatment Diabetic Retinopathy Study visual acuity, respectively, in patients with cystoid macular edema after cataract surgery (Irvine-Gass syndrome). METHODS: Fifteen eyes (15 patients) with a diagnosis of cystoid macular edema related to Irvine-Gass syndrome underwent ocular ophthalmologic examinations including Early Treatment Diabetic Retinopathy Study visual acuity and macular morphology assessment by spectral-domain optical coherence tomography. An observational period of 3 months after surgery was considered before starting therapy with oral acetazolamide and topical indomethacin. Patients' eyes were tested at baseline and at 3, 6, and 12 months posttreatment by spectral-domain optical coherence tomography and Early Treatment Diabetic Retinopathy Study visual acuity. Repeated measures analysis of variance was used to compare mean values. RESULTS: Mean (±SD) central macular thickness by spectral-domain optical coherence tomography was 530 (±98.1), 385.6 (±55.1), 339 (±32.3), and 316.2 (±27.0) µm at baseline, 3, 6, and 12 months of follow-up, respectively (P < 0.001). Mean (±SD) Early Treatment Diabetic Retinopathy Study visual acuity was 0.6 (±0.2), 0.2 (±0.1), 0.16 (±0.1), and 0.09 (±0.07) logarithm of the minimum angle of resolution at baseline, 3, 6, and 12-month follow-up, respectively (P < 0.001). Macular thickness changes were positively correlated (r = 0.75; P < 0.001) with visual acuity changes. Eyes with interruption of inner segment/outer segment junction at baseline (n = 3, 20%) showed a persistent damage of the photoreceptor junction and incomplete visual acuity recovery at the end of follow-up. CONCLUSION: Spectral-domain optical coherence tomography detects retinal findings, including photoreceptor inner segment/outer segment junction abnormalities that are correlated with visual acuity changes in treated patients with Irvine-Gass syndrome.

Effectiveness of hyaluronic acid and arnica extract ophthalmic solution in reducing dry eye symptoms in pediatric population.

AIM: to assess the effectiveness of a new combination of topical solution with Hyaluronic Acid 0.2% and arnica extract 0.1% in reducing dry eye symptoms in a population of pediatric patients. METHODS: 52 pediatric patients (aged 9 to 14 years) with signs and symptoms of dry eyes and allergic conjunctivitis were included in the study. Twenty-six patients were assigned to the Hyaluronic Acid 0.2%/ Arnica extract 0.1% group (Study Group) while 26 patients to the Hyaluronic Acid 0.2% group (Control Group). Clinical signs and symptoms were assessed at baseline and at week 4. The assessment plan included: slit-lamp examination, tear film break up time (TBUT), Schirmer's test and conjunctival hyperemia score. Ocular surface disease index (OSDI) score was used to evaluate subjective symptoms of dry eye disease. RESULTS: Both treatment groups showed improvements in the estimated clinical parameters after treatment. OSDI score was significantly lower in both treatment groups (Study group p = 0.02; Control group p = 0.04) at the end of the follow up period. Improvements in TBUT, Schirmer's test results and conjunctival hyperemia were statistically significant only in the Study group (p = 0.021; p = 0.03; p < 0.01 respectively). CONCLUSIONS: Preliminary findings suggest that combined topical Hyaluronic Acid 0.2% and arnica extract 0.1% can be effective in reducing symptoms and signs of dry eye disease in children.

Comparative analysis of visual outcomes of multifocal and monofocal intraocular lenses in congenital cataract surgery.

PURPOSE: To assess the impact on visual development of multifocal vs monofocal intraocular lenses (IOLs) implantation in children after congenital cataract surgery. SETTING: Ophthalmology Department, Bambino Gesù Children's Hospital, Rome, Italy. DESIGN: Retrospective interventional consecutive case series. METHODS: Records of 56 eyes of 43 pediatric patients who underwent congenital cataract surgery with phacoaspiration and simultaneous implantation of the IOL younger than 1 year were reviewed. Corrected distance visual acuity (CDVA), refractive error, and ocular motility disorders were evaluated at follow-up of greater than 4 years. RESULTS: 32 multifocal (18 unilateral, Group A and 14 bilateral, Group B) and 24 monofocal (12 unilateral, Group C and 12 bilateral, Group D) IOLs were implanted. Mean follow-up was 6.67 years. Mean CDVA of the eyes with multifocal IOLs was 0.75 ± 0.46 logMAR in unilateral cataract surgery and 0.34 ± 0.25 logMAR in bilateral ones; with monofocal IOLs was 0.71 ± 0.52 logMAR in unilateral and 0.53 ± 0.43 logMAR in bilateral ones. No statistically significant difference in the CDVA between Groups A and B and Groups C and D were recorded. Final mean spherical equivalent was -3.88 ± 4.73 diopters (D); in Group A, it was -2.74 ± 4.22 D, in Group C was -1.08 ± 1.45 D, in Group B was -4.82 ± 4.64 D, and in Group D was -6.81 ± 4.61 D. The difference was statistically significant between Groups B and D (P = .01), but not between Groups A and C (P = .14). 26 patients (60.4%) showed postoperative strabismus. Surgical correction occurred more in patients with multifocal IOLs implanted (P = .038). CONCLUSIONS: Multifocal IOLs did not show significant advantages in visual development in children after congenital cataract extraction younger than 1 year when compared with monofocal IOLs.

Treatment of Advanced Coats' Disease With Combination Therapy of Laser Photocoagulation, Intravitreal Ranibizumab, and Sub-Tenon Methylprednisolone Acetate.

PURPOSE: To investigate the efficacy of combination therapy with laser photocoagulation, intravitreal ranibizumab, and sub-Tenon methylprednisolone acetate in patients presenting with advanced Coats' disease. METHODS: This was a retrospective analysis of 16 patients who underwent laser photocoagulation combined with intravitreal ranibizumab and sub-Tenon methylprednisolone acetate between 2008 and 2017. The primary outcome was anatomic success and the secondary outcomes were globe preservation and final visual acuity. RESULTS: The average age at surgery was 5.12 ± 2.7 years (range: 3 to 10 years). The mean follow-up time was 45.43 ± 29.01 months (range: 12 to 108 months). Of the 16 patients (16 eyes) reviewed, 6 patients had stage 3A and 10 patients had stage 3B Coats' disease. The mean number of applications was 10 (range: 4 to 18). Globe preservation was achieved in all patients. Final visual acuity outcomes were satisfactory: 20/20 to 20/50 in 2 patients, 20/60 to 20/100 in 1 patient, and 20/200 or worse in 13 patients. CONCLUSIONS: Intravitreal ranibizumab used in combination with laser photocoagulation and sub-Tenon methylprednisolone acetate could be an effective treatment option for patients with advanced Coats' disease. The combined therapy achieved anatomical success, globe preservation, and reasonable visual acuity outcomes. [J Pediatr Ophthalmol Strabismus. 2022;59(3):187-191.].

PM10 prediction for brake wear of passenger car during different test driving cycles.

PM10 emissions generated from the brake wear of passenger car per braking event during three test driving cycles (WLTP, LACT, and WLTP-Brake) were studied using a finite element analysis (FEA) approach in combination with the relationship among the mass emitted rate of airborne particles versus local contact pressure and sliding speed. In addition, PM10 emissions were measured per braking event during the WLTP-Brake cycle on a brake dynamometer using an electrical low-pressure impactor (ELPI+) to validate the proposed FEA approach. The simulated and experimental results for WLTP-Brake illustrated that the proposed simulation approach has the potential to predict PM10 from brake wear per braking event, with an R2 value of 0.93. The FEA results of three test driving cycles showed that there was a gradient rise in pad wear on both sides from the inner to outer radii. The simulated PM10 emission factors during the WLTP, LACT, and WLTP-Brake were 7.9 mg km-1 veh-1, 9.8 mg km-1 veh-1, and 6.4 mg km-1 veh-1, respectively. Among three test driving cycles, the ratio of PM10 to total brake wear mass per braking event was the largest for the LACT, followed by WLTP and WLTP-Brake. From a practical application perspective, reducing the frequency of high-speed braking may be an effective way to decrease the generation of PM10 emissions.

Comparative analysis of non-exhaust airborne particles from electric and internal combustion engine vehicles.

This paper evaluates the effect of the electrification of the small, medium, and large internal combustion engine (ICE) passenger cars on the levels of total particulate matter (PM). The total mean PM10 and PM2.5 emission factors (EFs) on urban, rural, and motorway roads are in the range of 26.13 - 39.57 mg km-1 veh-1 and 13.39 - 18.44 mg km-1 veh-1, respectively, from small to large ICE passenger cars. Correspondingly, the total mean PM10 and PM2.5 non-exhaust EFs on urban, rural, and motorway roads range from 27.76 to 43.43 mg km-1 veh-1 and 13.17 -19.24 mg km-1 veh-1 from equivalent small to large electric vehicles (EVs) without regenerative braking. These results show that the total non-exhaust PM from the equivalent EVs may exceed all PM from ICE passenger cars, including exhaust particle emissions, which are dependent mainly on the extent of regenerative braking, followed by passenger car type and road type. PM10 EFs for equivalent EVs without regenerative braking on urban, rural, and motorway roads are all higher than those from ICE cars. As for PM2.5, most of the equivalent EVs require different extents of regenerative braking to reduce brake emissions to be in line with all particle emissions from relative ICE cars.

Implementation and microbiological stability of dose-banded ganciclovir infusion bags prepared in series by a robotic system.

OBJECTIVES: The implementation of dose-banding (DB) in centralised, pharmacy-based cytotoxic drug preparation units allows the preparation of standardised doses in series. The aim of this study was to evaluate the feasibility of DB for the prescribing of ganciclovir (GV) infusion solutions and to investigate the microbiological stability of dose-banded, automatically prepared ready-to-administer GV infusion bags by media-fill simulation tests and sterility tests. METHODS: The frequency of prescription of GV doses was retrospectively analysed before and after implementing the DB scheme. Four dose-ranges or 'bands' and the corresponding standard doses (250, 300, 350, 400 mg) were identified. The maximum variance was set at ±10% of the individually prescribed dose. The aseptic preparation of a series of GV infusion bags was simulated with double strength tryptic soy broth as growth medium and prefilled 0.9% NaCl polyolefin infusion bags as primary packaging materials. The simulation process was performed with the APOTECAchemo robot on five consecutive days. In total, 50 infusion bags were filled, incubated and stored for 12 weeks at room temperature. The media-filled bags were visually inspected for turbidity after 2, 4, 8, 10 and 12 weeks. Following incubation, growth promotion tests were performed. During the simulation tests, airborne contamination was monitored with settle plates and microbial surface contamination with contact plates. Pooled sterility tests were performed for a series of 10 standard GV infusion bags after a 12-week storage period under refrigeration (2 °C-8 °C). RESULTS: After implementation of the DB scheme, about 60% of the prescribed GV doses were prepared as standard preparations by the robotic system. The number of different GV doses was reduced by 61.8% (76 vs 29). None of the 50 media-filled bags showed turbidity after a storage period of 12 weeks, indicating the absence of microorganisms. The environmental monitoring with settle/contact plates matched the recommended limits set for cleanroom Grade A zones, except in the loading area of the robot. Media fills used for the sterility tests remained clear during the incubation period, thereby revealing sterility. Positive growth promotion tests proved the process's reliability. CONCLUSIONS: A DB scheme for prescribing and preparation of standard GV infusion bags was successfully implemented. Microbiological tests of aseptic preparation of infusion bags in series by the APOTECAchemo robot revealed an adequate level of sterility and a well-controlled aseptic procedure. The sterility was maintained over extended storage periods, thereby encouraging extended beyond-use dating.

Ocular manifestations and viral shedding in tears of pediatric patients with coronavirus disease 2019: a preliminary report.

PURPOSE: To evaluate ocular manifestations and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) prevalence in the tears of children with coronavirus disease 2019 (COVID-19). METHODS: A total of 27 pediatric patients with confirmed COVID-19 infection hospitalized from March 16 to April 15, 2020, at the Bambino Gesù Children's Hospital were enrolled in the study. At admission, all patients showed ocular manifestations. Reverse transcriptase-polymerase chain reaction from nasopharyngeal and conjunctival swabs were performed every 2-3 days before discharge. RESULTS: Of the 27 patients, 4 (15%) were asymptomatic, 15 (56%) showed respiratory symptoms, and 8 (30%) had gastrointestinal symptoms. At admission, nasopharyngeal swabs were positive for COVID-19 in all patients; on the second swabs, 7 children (26%) tested negative, and 20 remained positive for COVID-19. Ocular manifestations consistent with mild viral conjunctivitis were observed in 4 patients (15%). At first conjunctival swab, 3 patients (11%), 1 symptomatic and 2 asymptomatic for ocular infection, had positive findings for COVID-19; 2 became negative on the second test and 1 on the third. CONCLUSIONS: In our study cohort, ocular manifestations of COVID-19 seem to have had a milder clinical course in pediatric patients than in adults. Despite the low prevalence and rapid regression of viral presence in the conjunctiva, SARS-CoV-2 transmission through tears may be possible, even in patients without apparent ocular involvement.

Short-Term Assessment of Intravitreal Dexamethasone Implant Using Enhanced-Depth Image Optical Coherence Tomography and Optical Coherence Tomography Angiography in Patients with Retinal Vascular Diseases.

INTRODUCTION: To evaluate the short-term efficacy and safety of intravitreal dexamethasone implant (IDI) in patients with macular oedema associated with diabetic retinopathy (DR) and retinal vein occlusion (RVO) using enhanced-depth image optical coherence tomography (EDI-OCT) and to estimate the effect of dexamethasone on the choroid and the retinal vascular network using OCT angiography (OCTA). METHODS: Fifteen eyes in 15 patients with macular oedema secondary to diabetes (DR, n = 8) or retinal vein occlusion (RVO, n = 7) were treated with intravitreal injection of sustained-release IDI. Primary efficacy end points were changes in best corrected visual acuity and central macular thickness (CMT). Secondary end points were changes in choroidal thickness and choroidal and retinal vascular networks as determined by OCTA. RESULTS: CMT was significantly reduced from baseline by 3 h after injection (p < 0.01) and improved further during the 3-month follow-up. Visual acuity improvement was consistent with CMT reduction. No alterations in IOP or systemic side effects were observed. OCTA showed improvement from baseline in terms of decreased number and size of cysts and restoration of the retinal vascular network; flow choroidal thickness did not change significantly. CMT and visual acuity variations were similar in the two groups. CONCLUSIONS: CMT reduced as early as 3 h after the injection of IDI, with further reduction during follow-up. Choroidal thickness was unchanged, whereas the vascular retinal network improved from baseline to the end of study. Both EDI-OCT and OCTA were useful in demonstrating the early beneficial effects of IDI on the macula and the perifoveal vascular network. FUNDING: The article processing charges, the open access fee and the medical writing and editorial assistance was funded by Allergan.

Effect of intravitreal dexamethasone on macular edema in von Hippel-Lindau disease assessed using swept-source optical coherence tomography: a case report.

BACKGROUND: Von Hippel-Lindau disease is a rare hereditary syndrome caused by germinal mutations in a von Hippel-Lindau tumor-suppressing gene. Retinal hemangioblastoma is the ocular hallmark lesion of von Hippel-Lindau disease. CASE PRESENTATION: A 20-year-old Caucasian woman presented to our institution with painless visual impairment in the right eye. A fundus ophthalmoscopic evaluation and swept-source optical coherence tomographic examination revealed a retinal hemangioblastoma associated with cystoid macular edema. On the basis of the clinical ocular findings and genetic analysis, von Hippel-Lindau disease was diagnosed. Following an intravitreal injection of ranibizumab, off-label administration of intravitreal dexamethasone was considered to reduce the edema. An almost complete resolution of the edema in the macular area was observed 1 week after the injection. Finally, laser photocoagulation and transconjunctival cryotherapy were performed; the patient developed "ablatio fugax" after cryotherapy. CONCLUSIONS: In our experience, intravitreal dexamethasone administration has proven to be a useful tool for reducing retinal hemangioblastoma-related macular edema in von Hippel-Lindau disease and may be considered a potentially valuable treatment that can be used in combination with other therapies.

Swept source optical coherence tomography and optical coherence tomography angiography in pediatric enhanced S-cone syndrome: a case report.

BACKGROUND: Enhanced S-cone syndrome is an autosomal recessive retinal dystrophy related to a defect in a nuclear receptor gene (NR2E3) that leads to alteration in cells development from rod to S-cone. This retinal dystrophy may be associated with retinal schisis. The aim of this report is to describe structural optical coherence tomography and optical coherence tomography angiography features in a case of enhanced S-cone syndrome associated with macular schisis. CASE PRESENTATION: A Caucasian 13-year-old girl underwent measurement of best corrected visual acuity, ophthalmoscopic evaluation, and fundus autofluorescence examination. Photopic and scotopic electroretinography were carried out as well. Enhanced S-cone syndrome was suspected on the basis of clinical and electrophysiological findings. Structural optical coherence tomography and optical coherence tomography angiography allowed the further characterization of the associated macular schisis. Genetic analysis not only confirmed the diagnosis but increased the clinical novelty of this case report by showing two variations in the NR2E3 gene probably related to the phenotype: a missense variation c.1118T>C which leads to the substitution of leucine with proline in amino acid position 373, and c.349+5G>C, which involves a gene sequence near a splicing site. CONCLUSIONS: Swept source structural optical coherence tomography (B scans and "en face" images) and optical coherence tomography angiography allowed the observation of retinal structural details and the involvement of each retinal layer and capillary plexus in enhanced S-cone syndrome. Of interest, neither of the two NR2E3 gene variants found in this case report have been linked to any form of retinopathy.

Choroidal Thickness Changes After Intravitreal Ranibizumab for Exudative Age-Related Macular Degeneration.

BACKGROUND: The results regarding changes of choroidal thickness following intravitreal ranibizumab injections in the literature are controversial. Vascular endothelial growth factor A is implicated in pathogenesis of neovascular age-related macular degeneration (AMD). The suspected unchanged choroidal layer thickness after intravitreal injections of ranibizumab suggests a possible protection of the outer blood-retinal barrier in the human eye. OBJECTIVE: The aim was to evaluate choroidal thickness following the first administration of the study drug ranibizumab into the eyes of naïve wet AMD patients (nAMD). METHODS: In this open label, 3-month, prospective, single-center, interventional, single-arm pilot study, 20 nAMD eyes were included and underwent three consecutive monthly injections of ranibizumab (0.5 mg/0.05 ml). Vital signs (i.e., blood pressure and pulse), ophthalmic examinations, intraocular pressure, best correct visual acuity and subfoveal choroidal thickness as examined with optical coherence tomography using enhanced depth imaging (OCT-EDI) were assessed at each visit. All patients were evaluated at baseline and at 15, 30 60 and 90 days after intravitreal injection. Ten eyes with fibrotic AMD lesions were evaluated as the control group. RESULTS: In all eyes, the choroidal thicknesses (µm) exhibited no significant changes from the baseline visit to the visits at 15, 30, 60 and 90 days post-injection (P > 0.05). The intravitreal treatment with ranibizumab was well tolerated, and no adverse events were registered. CONCLUSION: Choroidal thickness appeared to be unmodified following the intravitreal injection of ranibizumab into nAMD eyes. Intravitreal ranibizumab injections probably elicit a pharmacologic effect only in the choroidal neovascularization and not in the choroid circulation under neovascular lesions. Clinical Trials Eudract Registration #: 2013-005091-17.