The Antibacterial Efficacy of High-Fluence PACK Cross-Linking Can Be Accelerated.

Purpose: To determine whether high-fluence photoactivated chromophore for keratitis cross-linking (PACK-CXL) can be accelerated. Methods: Solutions of Staphylococcus aureus and Pseudomonas aeruginosa with 0.1% riboflavin were prepared and exposed to 365 nm ultraviolet (UV)-A irradiation of intensities and fluences from 9 to 30 mW/cm2 and from 5.4 to 15.0 J/cm2, respectively, representing nine different accelerated PACK-CXL protocols. Irradiated solutions and unirradiated controls were diluted, plated, and inoculated on agar plates so that the bacterial killing ratios (BKR) could be calculated. Additionally, strains of Achromobacter xylosoxidans, Staphylococcus epidermidis, and Stenotrophomonas maltophilia were exposed to a single accelerated PACK-CXL protocol (intensity: 30 mW/cm2, total fluence: 15.0 J/cm2). Results: With total fluences of 5.4, 10.0, and 15.0 J/cm2, the range of mean BKR for S. aureus was 45.78% to 50.91%, 84.13% to 88.16%, and 97.50% to 99.90%, respectively; the mean BKR for P. aeruginosa was 69.09% to 70.86%, 75.37% to 77.93%, and 82.27% to 91.44%, respectively. The mean BKR was 41.97% for A. xylosoxidans, 65.38% for S. epidermidis, and 78.04% for S. maltophilia for the accelerated PACK-CXL protocol (30 mW/cm2, 15 J/cm2). Conclusions: The BKR of high-fluence PACK-CXL protocols can be accelerated while maintaining a high, but species-dependent, BKR. The Bunsen to Roscoe law is respected in fluences up to 10 J/cm2 in S. aureus and P. aeruginosa, whereas fluences above 10 J/cm2 show strain dependence. Translational Relevance: The high-fluence PACK-CXL protocols can be accelerated in clinical practice while maintaining high levels of BKR.

Individualized Corneal Cross-linking With Riboflavin and UV-A in Ultrathin Corneas: The Sub400 Protocol.

PURPOSE: To determine whether corneal cross-linking (CXL) with individualized fluence ("sub400 protocol") is able to stop keratoconus (KC) progression in ultrathin corneas with 12-month follow-up. DESIGN: Retrospective, interventional case series. METHODS: Thirty-nine eyes with progressive KC and corneal stromal thicknesses from 214 to 398 µm at the time of ultraviolet irradiation were enrolled. After epithelium removal, ultraviolet irradiation was performed at 3 mW/cm2 with irradiation times individually adapted to stromal thickness. Pre- and postoperative examinations included corrected distance visual acuity (CDVA), refraction, Scheimpflug, and anterior segment optical coherence tomography imaging up to 12 months after CXL. Outcome measures were arrest of KC progression at 12 months postoperatively and stromal demarcation line (DL) depth. RESULTS: Thirty-five eyes (90%) showed tomographical stability at 12 months after surgery. No eyes showed signs of endothelial decompensation. A significant correlation was found between DL depth and irradiation time (r = +0.448, P = .004) but not between DL depth and change in Kmax (r = -0.215, P = .189). On average, there was a significant change (P < .05) in thinnest stromal thickness (-14.5 ± 21.7 µm), Kmax (-2.06 ± 3.66 D) and densitometry (+2.00 ± 2.07 GSU). No significant changes were found in CDVA (P = .611), sphere (P = .077), or cylinder (P = .915). CONCLUSIONS: The "sub400" individualized fluence CXL protocol standardizes the treatment in ultrathin corneas and halted KC progression with a success rate of 90% at 12 months. The sub400 protocol allows for the treatment of corneas as thin as 214 µm of corneal stroma, markedly extending the treatment range. The DL depth did not predict treatment outcome. Hence, the depth is unlikely related to the extent of CXL-induced corneal stiffening but rather to the extent of CXL-induced microstructural changes and wound healing.

Contribution of Bowman layer to corneal biomechanics.

PURPOSE: To compare the elastic modulus of thin corneal lamellas using 2D stress-strain extensometry in healthy ex vivo human corneal lamellas with or without the presence of Bowman layer. SETTING: Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Switzerland; ELZA Institute, Dietikon, Switzerland; Department of Ophthalmology, Philipps University of Marburg, Germany. DESIGN: Prospective experimental laboratory study. METHODS: Healthy human corneas were stripped of Descemet membrane and the endothelium for Descemet membrane endothelial keratoplasty. After epithelium removal, corneas were divided into 2 groups. In Group 1, Bowman layer was ablated with an excimer laser (20 µm thick, 10 mm). In Group 2, Bowman layer was left intact. Then, a lamella was cut from the anterior cornea with an automated microkeratome. Elastic and viscoelastic material properties were analyzed by 2D stress-strain extensometry between 0.03 and 0.70 N. RESULTS: Twenty-six human corneas were analyzed. The mean lamella thickness was 160 ± 37 µm in corneas with Bowman layer and 155 ± 22 µm in corneas without. No statistically significant differences between flaps with and without Bowman layer were observed in the tangential elastic modulus between 5% and 20% strain (11.5 ± 2.9 kPa vs 10.8 ± 3.7 kPa, P > .278). CONCLUSIONS: The presence or absence of Bowman layer did not reveal a measurable difference in corneal stiffness. This may indicate that the removal of Bowman layer during photorefractive keratectomy does not represent a disadvantage to corneal biomechanics.

Assessment of the mechanical forces applied during eye rubbing.

BACKGROUND: To determine the average amount of mechanical forces applied to the lids of keratoconus patients during eye rubbing. METHODS: Fifty-seven patients (41 male, 16 female, average age 34.8 years) with a clinically and topographically diagnosed keratoconus and a history of eye rubbing were prospectively asked to perform their individual eye rubbing movement on a high-precision balance. The type of eye-rubbing movement and the force applied, represented in newtons (N), were recorded and analyzed. RESULTS: We detected three different types of eye rubbing. Rubbing with the fingertip was most frequent (51%), followed by rubbing with the knuckle (44%) and rubbing with the fingernail (6%). Each type of eye rubbing showed different average forces, with knuckle type eye rubbing applying significantly more force (9.6 ± 6.3 N) on the lids than fingertip (4.3 ± 3.1 N) and fingernail (2.6 ± 3.3 N) types (p < 0,001 and p = 0,016, respectively). CONCLUSIONS: There were major variations in the force exerted on the lids, depending on the type of eye rubbing employed. This data will help determine the forces that need to be applied in future experimental eye rubbing models.

Severe Phenotype in a Patient With Homozygous 15q21.2 Microdeletion Involving BCL2L10, GNB5, and MYO5C Genes, Resembling Infantile Developmental Disorder With Cardiac Arrhythmias (IDDCA).

Homozygous and compound heterozygous mutations in GNB5 gene have been associated with a wide spectrum of clinical presentations, ranging from neurodevelopmental issues with or without cardiac arrhythmia (LADCI) to severe developmental delay with epileptic encephalopathy, retinal dystrophy, and heart rhythm abnormalities (IDDCA). While missense or missense/non-sense mutations usually lead to milder form, the biallelic loss of function of GNB5 gene causes the severe multisystemic IDDCA phenotype. So far, only 27 patients have been described with GNB5-associated disease. We report the first case of a patient carrying a homozygous 15q21.2 microdeletion, encompassing GNB5 and the two contiguous genes BCL2L10 and MYO5C. The clinical features of the child are consistent with the severe IDDCA phenotype, thus confirming the GNB5 loss-of-function mechanism in determining such presentation of the disease.

Similar Biomechanical Cross-linking Effect After SMILE and PRK in Human Corneas in an Ex Vivo Model for Postoperative Ectasia.

PURPOSE: To evaluate the biomechanical effect of corneal cross-linking (CXL) in paired human corneas following small incision lenticule extraction (SMILE) or photorefractive keratectomy (PRK) in an ex vivo model for postoperative ectasia. METHODS: Twenty-six paired human corneas preserved in tissue culture medium were equally divided into two groups: right and left corneas were treated with PRK and SMILE, respectively. Corneal thickness was measured in all eyes before surgery. Corneas were stretched using an extensometer with two cycles of up to 9 N (570 kPA stress), followed by accelerated CXL with irradiance of 9 mW/cm2 for 10 minutes (fluence 5.4 J/cm2) in both groups. The elastic modulus was evaluated using two-dimensional stress-strain extensometry. RESULTS: Following accelerated CXL, the ectatic cornea model showed a mean effective elastic modulus of 17.2 ± 5.3 MPa after PRK and 14.1 ± 5.0 MPa after SMILE. Although the elastic modulus in corneas previously subjected to PRK was higher, there was no significant biomechanical difference between the two groups (P = .093). CONCLUSIONS: Under similar conditions, both experimental groups (PRK followed by CXL and SMILE followed by CXL) were characterized by similar biomechanical stability as measured experimentally on ex vivo human fellow corneas. The data suggest that, in the event of postoperative ectasia, the biomechanical improvement achieved by CXL may be similar after PRK and SMILE. [J Refract Surg. 2020;36(1):49-54].

A case of acute exudative polymorphous vitelliform maculopathy: follow-up and wide-field spectral-domain optical coherence tomography.

PURPOSE: To present a case of an HIV-positive patient with acute exudative polymorphous vitelliform maculopathy (AEPVM) and evaluate the presence of specific spectral-domain optical coherence tomography (SD-OCT) findings. METHODS: Case report. RESULTS: We reviewed the AEPVM cases reported in the literature and compared those to our patient to determine if there is a correspondence between the etiology that leads to the onset of AEPVM and clinical and SD-OCT findings. CONCLUSIONS: Acute exudative polymorphous vitelliform maculopathy is a disease that involves the outer retinal layers with lipofuscin deposits and serous detachment of the neuroepithelium with or without intraretinal cysts. Not much is known about the etiology and pathogenesis, and not many cases have been described. A review of the few clinical cases reported in the literature does not show a specific correspondence between etiology and SD-OCT findings.

Spectral-domain optical coherence tomography measurements of central foveal thickness before and after cataract surgery in children.

PURPOSE: To compare macular thickness before and after cataract surgery and intraocular lens (IOL) implantation in pediatric eyes. DESIGN: Retrospective cohort study. SETTING: University Eye Clinic, San Giuseppe Hospital, University of Milan, Milan, Italy. METHODS: The study analyzed spectral-domain optical coherence tomography (SD-OCT) images of the macula in pediatric eyes in which cataract surgery had been performed and that were examined preoperatively and 1, 3, 6, 9, and 12 months postoperatively. RESULTS: The mean age of the 11 patients (11 eyes) was 5.8 years ± 2.2 (SD) (range 3 to 14 years). The mean macular thickness at 1 month and 3 months was significantly higher than at baseline (273.7 ± 26.8 µm and 266.0 ± 22.8 µm, respectively, versus 244.8 ± 19.5 µm; P < .0001). It reached the baseline value after 3 months and remained stable over the 12-month follow-up. The mean thicknesses at 6, 9, and 12 months were 249.1 ± 17.6 µm, 245.7 ± 18.5 µm, and 246.2 ± 18.1 µm, respectively (P > .05 versus baseline). CONCLUSIONS: Spectral-domain OCT was useful in evaluating the macular changes in the eyes of a cohort of pediatric patients 3 years and older. Cystoid macular edema was not observed during the 12-month follow-up. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Spectral-domain optical coherence tomography findings in pediatric tilted disc syndrome.

PURPOSE: To report a novel spectral-domain optical coherence tomography (SD-OCT) finding in children affected by tilted disc syndrome (TDS), and to correlate it with early visual field defects. METHODS: Patients between 5 and 17 years old with TDS were enrolled in this study. The diagnosis of TDS was made by stereoscopic fundus photography, when the upper edge of the optic disc protruded anteriorly relative to its lower edge. All eyes were examined with 12 radial SD-OCT B-scans of 12 mm centered on the optic disc; the fundus area encompassing the optic nerve was additionally scanned using several vertical and horizontal scans.. C-scan SD-OCT were acquired using the Macular Cube 512 x 128 to create the en face image. Standard automated perimetry 24-2 tests were performed on all patients. RESULTS: Thirty-eight eyes of 20 pediatric patients with TDS syndrome were enrolled during this 24-months clinical trial. Their mean age was 10.9 ± 2.7 years (range 7-15 years), 12 (60%) were male and eight (40%) were female. The OCT images of the optic discs showed a protrusion of the upper edge of Bruch's membrane and choroid at the nasal edge of the optic disc in 39.5% of the eyes. The retinal nerve fiber tissue appeared to be herniated into this protrusion and bent superiorly in 15 eyes. This severe bending corresponded to early visual field anomalies that were not reduced by corrective lenses in 46.7% of the eyes. CONCLUSION: Visual field defects that do not improve by increased myopic correction in TDS may be due to the severe bending of the retinal nerve fiber tissue, which would impair axonal flow.

Efficacy of intravitreal dexamethasone implant for prostaglandin-induced refractory pseudophakic cystoid macular edema: case report and review of the literature.

BACKGROUND: Macular edema is a known complication even after uneventful cataract surgery. The chronic use of prostaglandin analogs is a risk factor for the development of pseudophakic cystoid macular edema (CME). Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered first-line therapy but refractory postsurgical CME represents a therapeutic challenge, as there is not an evidence-based treatment. OBJECTIVE: To report the use of a single implant of intravitreal dexamethasone for tafluprost-associated pseudophakic CME refractory to NSAIDs and to sub-Tenon's corticosteroid injections. CASE REPORT: A 64-year-old female with ocular hypertension treated with tafluprost experienced decreased vision (visual acuity 20/60) and metamorphopsia 2 months after uneventful cataract extraction. Spectral domain optical coherence tomography (SD-OCT) revealed CME. After 1 month of topical and oral NSAIDs, CME was still evident on SD-OCT (visual acuity 20/50). Two sub-Tenon's betamethasone injections were performed at a 2-week interval. As CME was still present, 2 months after the diagnosis of CME (visual acuity 20/40), the patient underwent a single dexamethasone intravitreal implant. One month later, macular appearance was normal, and visual acuity increased to 20/30. This result was maintained throughout the 6 months of follow-up. CONCLUSION: In this report, a single implant of intravitreal dexamethasone successfully treated pseudophakic CME associated with the use of prostaglandin analogs unresponsive to NSAIDs and sub-Tenon's betamethasone. The results of this report need to be corroborated by powered, prospective, randomized trials. The need for repeated treatments as well as the retreatment interval in patients requiring more than a single injection are issues still needing further investigations.