Transepithelial Enhanced Fluence Pulsed Light M Accelerated Crosslinking for Early Progressive Keratoconus with Chemically Enhanced Riboflavin Solutions and Air Room Oxygen.

PURPOSE: To assess the 3-year clinical results of the 18 mW 7 J/cm2 transepithelial enhanced fluence pulsed light M accelerated crosslinking in the treatment of progressive keratoconus (KC) with chemically enhanced hyper-concentrated riboflavin solutions without iontophoresis and with air-room oxygenation. SETTING: Siena Crosslinking Center, Siena, Italy. METHODS: Prospective pilot, open non-randomized interventional study including 40 eyes of 30 young adult patients over 21 years old (10 simultaneous bilateral) with early (Stage I and II) progressive KC undergoing TE-EFPL 18 mW/7 J/cm2 ACXL (EFPL M TECXL). The 12 min and 58 s pulsed light (1 s on/1 s off) UV-A exposure treatments were performed with a biphasic corneal soaking using Paracel I 0.25% for 4 min and Paracel II 0.22% for 6 min riboflavin solutions and New KXL I UV-A emitter (Glaukos-Avedro, Waltham, USA) at an air room of 21% oxygenation. All patients completed the 3-year follow-up. RESULTS: CDVA showed a statistically significant improvement in the third postoperative month (Δ + 0.17 d. e.) with a final gain of +0.22 d. eq. AK showed a statistically significant decrease in the sixth postoperative month (Δ - 1.15 diopters). K itmax showed a statistically significant decrease at 1-year follow-up (Δ - 1.3 diopters). The coma value improved significantly by the sixth month (Δ - 0.54 µm). MCT remained stable during the entire follow-up. No adverse events were recorded. Corneal OCT revealed a mean demarcation line depth at 282.6 ± 23.6 µm. CONCLUSIONS: Transepithelial enhanced fluence pulsed light M accelerated crosslinking with chemically enhanced riboflavin solution halted KC progression in young adult patients without iontophoresis and no intraoperative oxygen supplementation addressing the importance of increased fluence.

Long term results of accelerated 9 mW corneal crosslinking for early progressive keratoconus: the Siena Eye-Cross Study 2.

PURPOSE: To assess clinical results of the 9 mW/5.4 J/cm2 accelerated crosslinking (ACXL) in the treatment of progressive keratoconus (KC) over a span of 5 years. METHODS: The prospective open non-randomized interventional study (Siena Eye-Cross Study 2) included 156 eyes of 112 patients with early progressive KC undergoing the Epi-Off 9 mW/5.4 J/cm2 ACXL at the Siena Crosslinking Centre, Italy. The mean age was 18.05 ± 5.6 years. The 20-min treatments were performed using the New KXL I (Avedro, Waltham, USA), 10 min of 0.1% HPMC Riboflavin soaking (VibeX Rapid, Avedro, Waltham, USA) and 10 min of continuous-light UV-A irradiation. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), Kmax, coma, minimum corneal thickness (MCT), surface asymmetry index (SAI), endothelial cell count (ECC) were measured, and corneal OCT performed. RESULTS: UDVA and CDVA improved significantly at the 3rd (P = 0.028), Δ + 0.17 Snellen lines and 6th postoperative month, respectively (P < 0.001), Δ + 0.23 Snellen lines. Kmax improved at the 6th postoperative month (P = 0.03), Δ - 1.49 diopters from the baseline value. Also, coma aberration value improved significantly (P = 0.004). A mild temporary haze was recorded in 14.77% of patients without affecting visual acuity and without persistent complications. Corneal OCT revealed a mean demarcation line depth at 332.6 ± 33.6 µm. CONCLUSION: The 5-year results of Epi-Off 9 mW/5.4 J/cm2 ACXL demonstrated statistically significant improvements in UCVA and CDVA, corneal curvature and corneal higher-order aberrations which confers a long-term stability for progressive ectasia. Based on the results of the Siena Eye-Cross Study 2, the 9 mW/5.4 J/cm2 ACXL is a candidate to be  the natural evolution of Epi-Off CXL treatment for the management of early progressive corneal ectasia, and thus optimize clinic workflow.

Multimodal Imaging in Susac Syndrome: A Case Report and Literature Review.

Susac syndrome (SS) is a rare microangiopathy that involves arterioles of the brain, retina, and cochlea. Diagnosis is extremely difficult because of the rarity of the disease and because the signs and symptoms often occur at different times. Multidisciplinary approaches and multimodal images are mandatory for diagnosis and prompt therapy. In this report, we describe a case of SS and the application of multimodal retinal imaging to evaluate the ophthalmologic changes and to confirm diagnosis. Early diagnosis and therapy based on the associations of steroids and immunosuppressants are necessary to limit the sequelae of the disease.

Customized corneal crosslinking for treatment of progressive keratoconus: Clinical and OCT outcomes using a transepithelial approach with supplemental oxygen.

PURPOSE: To evaluate the outcomes of customized corneal crosslinking (CXL) for treatment of progressive keratoconus (KC) using a transepithelial approach with supplemental oxygen. SETTING: Siena Crosslinking Center, Siena, Italy. DESIGN: Prospective interventional case series. METHODS: Twenty-seven eyes of 24 patients (mean age 29.3 ± 7.3 years) with progressive KC underwent customized corneal CXL using a transepithelial approach with supplemental oxygen. Ultraviolet (UV)-A irradiation of 365 nm wavelength was delivered in an accelerated (30 mW/cm) pulsed-light UV light exposure in a 2-zone elliptical pattern. A total dose of 10 J/cm was delivered at the KC apex, surrounded by a broadbeam spot of 7.2 J/cm. After 0.25% riboflavin corneal soaking, the UV-A irradiation was initiated in the presence of additional oxygen (≥90% concentration) delivered through special goggles connected to an oxygen delivery system (flow-rate 2.5 liters per minute). Key outcome measures included corrected distance visual acuity (CDVA), keratometry (AK, K1, K2, and K-average), corneal higher-order aberrations, topographic and manifest cylinder, corneal optical coherence tomography (OCT) demarcation line, and endothelial cell count. RESULTS: Of the 27 eyes studied, a significant improvement of CDVA was recorded at 6-month follow-up visits, from baseline 0.19 ± 0.06 logarithm of the minimum angle of resolution (logMAR) to 0.11 ± 0.04 logMAR (P < .05). Significant flattening of steep keratometry (K2) was reported with mean change of -1.9 diopters (D) (P < .05), and coma values improved from 0.47 ± 0.28 µm to 0.28 ± 0.16 µm (P < .05). OCT revealed 2 demarcation lines at mean depths of 218.23 ± 43.32 µm and 325.71 ± 39.70 µm. CONCLUSIONS: In this series, customized CXL using a transepithelial approach with intraoperative supplemental oxygen resulted in clinically meaningful improvements in corneal curvature and CDVA without significant adverse events.

Intraconal Retro-Orbital B-Type Antoni Neurinoma Causing Vision Loss.

Schwannoma is a rare benign tumor, originating from Schwann cells of the peripheral nerve sheath. We describe a case of intraconal orbital schwannoma, causing compression to the optic nerve and progressive visual impairment treated with surgical resection. The diagnosis of benign orbital schwannoma was provided by histopathological examination (large spindle cell tumor with AntoniB-type cell pattern) and also with immunohistochemistry (positivity for S-100 protein). The 6 months' follow-up was performed. The patient was asymptomatic during the 6-month follow-up.

Iontophoresis Corneal Cross-linking With Enhanced Fluence and Pulsed UV-A Light: 3-Year Clinical Results.

PURPOSE: To assess 3-year safety and efficacy of enhanced-fluence pulsed-light iontophoresis cross-linking (EF I-CXL) in patients with progressive keratoconus. METHODS: This prospective interventional pilot study included 24 eyes of 20 patients, with a mean age of 23.9 years (range: 15 to 36 years). Iontophoresis with riboflavin solution was used for stromal imbibition. The treatment energy was optimized at 30% (7 J/cm2) and ultraviolet-A power set at 18 mW/cm2 × 6.28 minutes of pulsed-light on-off exposure, with a total irradiation time of 12.56 minutes. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), corneal tomography, and corneal optical coherence tomography (OCT) at baseline and 1, 3, 6, 12, 24, and 3 years postoperatively were evaluated. RESULTS: At 3 years, average UDVA decreased from 0.50 ± 0.10 to 0.36 ± 0.08 logMAR (P < .05), average maximum keratometry decreased from 52.94 ± 1.34 to 51.4 ± 1.49 diopters (D) (Delta: -1.40 ± 0.80 D; P < .05), average coma improved from 0.24 ± 0.05 to 0.12 ± 0.02 µm (P = .001), and symmetry index decreased from 4.22 ± 1.01 to 3.53 ± 0.90 D. Corneal OCT showed demarcation line detection at 285.8 ± 20.2 µm average depth in more than 80% at 1 month postoperatively. CONCLUSIONS: The 3-year results of EF I-CXL showed satisfactory I-CXL functional outcomes, increasing the visibility and the depth of demarcation line closer to epithelium-off standard CXL. [J Refract Surg. 2020;36(5):286-292.].

In vivo confocal microscopy: qualitative investigation of the conjunctival and corneal surface in open angle glaucomatous patients undergoing the XEN-Gel implant, trabeculectomy or medical therapy.

PURPOSE: Assessing the quality of the ocular surface by in vivo scanning laser confocal microscopy (IVCM) in primary open angle glaucoma (POAG) patients treated by Xen 45 Gel Stent, medical therapy and trabeculectomy. METHODS: Retrospective, single-center, single-masked, comparative study including 60 eyes of 30 patients (mean age 61.16 ± 10 years) affected by POAG. Eyes were divided into 3 groups: Group 1 eyes underwent the Xen 45 Gel Stent procedure, Group 2 eyes were under medical therapy, Group 3 eyes were surgically treated by trabeculectomy. All patients underwent HRT II IVCM analysis of cornea, limbus, conjunctiva, sub-tenionian space and sclera. RESULTS: The Xen 45 Gel stent, if properly positioned in the sub-conjunctival space preserves goblet cells and limits ocular surface inflammation. Regular corneal epithelial cells with micro-cysts, and normo-reflective sub-epithelial nerve plexus are documented by IVCM. In sub Tenon's implants an alternative lamellar intra-scleral filtration is detectable. Combined surgical procedures show a noticeable number of inflammatory cells with rare micro-cysts. Post-trabeculectomy inflammatory reaction is more evident than Xen 45 Gel Stent associated surgical procedures, but less than medical therapy where a conspicuous presence of Langerhans cells, peri-neural infiltrates, marked loss of goblet cells and fibrosis is visible. CONCLUSION: Ocular surface inflammation was more notable in topical therapy than after trabeculectomy, which itself causes more inflammation than XEN Gel stents.

Enhanced-Fluence Pulsed-Light Iontophoresis Corneal Cross-linking: 1-Year Morphological and Clinical Results.

PURPOSE: To assess the safety and efficacy of a novel pulsed-light enhanced-fluence iontophoresis corneal cross-linking (EF I-CXL) procedure in patients with progressive keratoconus. METHODS: This prospective interventional pilot study included 12 eyes of 10 patients. Iontophoresis with Ricrolin+ solution (Sooft, Montegiorgio, Italy) was used for stromal imbibition. The treatment energy dose (fluence) was optimized at 30% (from 5.4 J to 7 J/cm2) and ultraviolet-A (UV-A) power set at 18 mW/cm2 × 6.28 minutes of exposure time, pulsing the light 1 second on/1 second off with a total irradiation time of 12.56 minutes. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), Scheimpflug corneal tomography data, and corneal optical coherence tomography (OCT) at baseline and 1, 3, 6, and 12 months postoperatively were evaluated. RESULTS: Twelve-month statistically significant average data (P < .05) showed UDVA decreased from 0.50 ± 0.10 to 0.36 ± 0.08 logMAR, maximum keratometry decreased from 52.86 ± 1.50 to 51.49 ± 0.90 diopters (D), surface asymmetry index decreased from 2.34 ± 0.36 to 2.13 ± 1.12 D, symmetry index decreased from 4.22 ± 1.01 to 3.56 ± 0.90 D, and coma decreased from 0.25 ± 0.05 to 0.14 ± 0.06 µm. Corneal OCT showed greater than 80% demarcation line detection at 295.8 ± 20.2 µm depth on average in the first postoperative month. CONCLUSIONS: The preliminary results of the EF I-CXL protocol demonstrate its capability to increase I-CXL efficacy closer to standard CXL. [J Refract Surg. 2018;34(7):438-444.].

Accelerated 15 mW pulsed-light crosslinking to treat progressive keratoconus: Two-year clinical results.

PURPOSE: To assess the clinical and microstructural results of accelerated 15 mW pulsed-light corneal crosslinking (CXL) to treat progressive keratoconus. SETTING: Siena Crosslinking Center, Siena, Italy. DESIGN: Prospective case series. METHODS: After epithelium removal (with Epi-Clear) and 10 minutes stromal soaking with riboflavin 0.1% hydroxypropyl methylcellulose solution, all eyes had 15 mW/cm2 pulsed-light epithelium-off accelerated CXL for 6 minutes of ultraviolet-A (UVA) irradiation (1 second on/1 second off), maintaining a total UVA exposure of 12 minutes at a fluence of 5.4 J/cm2. The 2-year follow-up examination included uncorrected (UDVA) and corrected (CDVA) distance visual acuities, Scheimpflug tomography, in vivo confocal microscopy (IVCM), and spectral-domain optical coherence tomography (SD-OCT). RESULTS: The study comprised 132 eyes of 96 patients (mean age 23.7 years ± 4.3 [SD]) with stage II keratoconus. The change in UDVA and CDVA was statistically significant, from 0.51 ± 0.106 logarithm of the minimum angle of resolution (logMAR) at baseline to 0.309 ± 0.074 logMAR (P = .0001) and 0.271 ± 0.144 logMAR at baseline to 0.135 ± 0.100 logMAR (P = .0023), respectively. Coma values measured by Scheimpflug analysis showed a statistically significant improvement beginning with the first postoperative month (P = .0004). The IVCM scans documented basal epithelial healing occurring 72 hours after treatment associated with the presence of subepithelial nerves. The SD-OCT scans performed in the central 6.0 mm of corneal diameter documented a demarcation line at a mean depth of 280 ± 32 µm. CONCLUSION: The 15 mW/cm2 pulsed-light epithelium-off accelerated CXL was effective and safe, stabilizing keratoconus progression through 2 years of follow-up.

Blindness and Glaucoma: A Multicenter Data Review from 7 Academic Eye Clinics.

PURPOSE: To evaluate frequency, conversion rate, and risk factors for blindness in glaucoma patients treated in European Universities. METHODS: This multicenter retrospective study included 2402 consecutive patients with glaucoma in at least one eye. Medical charts were inspected and patients were divided into those blind and the remainder ('controls'). Blindness was defined as visual acuity≤0.05 and/or visual field loss to less than 10°. RESULTS: Unilateral and bilateral blindness were respectively 11.0% and 1.6% at the beginning, and 15.5% and 3.6% at the end of the observation period (7.5±5.5 years, range:1-25 years); conversion to blindness (at least unilateral) was 1.1%/year. 134 eyes (97 patients) developed blindness by POAG during the study. At the first access to study centre, they had mean deviation (MD) of -17.1±8.3 dB and treated intraocular pressure (IOP) of 17.1±6.6 mmHg. During follow-up the IOP decreased by 14% in these eyes but MD deteriorated by 1.1±3.5 dB/year, which was 5-fold higher than controls (0.2±1.6 dB/year). In a multivariate model, the best predictors for blindness by glaucoma were initial MD (p<0.001), initial IOP (p<0.001), older age at the beginning of follow-up (p<0.001), whereas final IOP was found to be protective (p<0.05). CONCLUSIONS: In this series of patients, blindness occurred in about 20%. Blindness by glaucoma had 2 characteristics: late diagnosis and/or late referral, and progression of the disease despite in most cases IOP was within the range of normality and target IOP was achieved; it could be predicted by high initial MD, high initial IOP, and old age.

Repeatability and reproducibility of applanation resonance tonometry: a cross-sectional study.

BACKGROUND: To assess repeatability (intra-observer variability) and reproducibility (inter-operator variability) of intraocular pressure (IOP) measurements with servo-controlled Bioresonator Applanation Resonance Tonometry (ART) and to evaluate possible influential factors. METHODS: The study included 178 patients (115 glaucoma and 63 controls; one eye per subject). IOP was measured once with a Goldmann applanation tonometer (GAT) and twice by ART (ART1, ART2), in randomized sequence, by a single operator to assess intra-operator variability. Each ART measurement consisted on 3 readings. To assess inter-operator variability 2 evaluators performed 2 measurements each (in random order) on the same patient. Repeatability and reproducibility were assessed by the coefficient of variation (CoV) and intraclass correlation coefficient (ICC). RESULTS: In the entire cohort, ART1 was 0.4 ± 2.2 mmHg (-7.0 to 5.7 mmHg) higher than ART2 (p = 0.03) regardless of test order. Intra-operator CoV was 7.0% ± 6.3%, and ICC was 0.80-0.92. Inter-operator CoV ranged between 5.7% ± 6.1% and 8.2% ± 7.2%, and ICC between 0.86 and 0.97. ART1 and 2 were respectively 1.7 ± 3.1 and 1.3 ± 3.1 mmHg higher than GAT (p < 0.01). Test-retest difference with ART fell within ±1 mmHg in 41% of cases, within ±2 mmHg in 70%, within ±3 mmHg in 85%. 15% had a test-retest difference higher than ± 3 mmHg; Bland-Altman 95% intervals of confidence were -3.9 and +4.6 mmHg. Results were unaffected by age, diagnosis, central corneal thickness, keratometry, operator, randomization sequence. CONCLUSIONS: In most cases ART repeatability and reproducibility were high, with no differences due to patients' characteristics. ART measurements overestimated GAT by a mean of 1.3-1.7 mmHg.