Faculty Bibliography

Before the advent of modern tomographic imaging and corneal cross-linking (CXL), diagnosis and treatment of ectatic disease were limited to disease severity where changes on the anterior corneal surface lead to visual complaints. Rigid contact lenses and/or penetrating keratoplasty addressed late stage disease, as identifying early or subclinical disease was not possible, or its need appreciated. The emergence of CXL as a viable treatment to alter the natural progression of keratoconus heightened the need for improved diagnostics.Several methods have been described in the literature to evaluate and document progression in keratoconus, but there has been no consistent definition of ectasia progression. Newer imaging techniques (ie, tomography) allowed the detection of earlier ectatic disease, before visual loss and subjective complaints. The Belin ABCD classification/staging system was introduced on a Scheimpflug imaging system [Pentacam, (Oculus GmbH, Wetzlar, Germany)] to address previous shortcomings. The ABCD system utilizes 4 parameters: Anterior ("A") and posterior ("B" for Back) radius of curvature taken from a 3.0 mm optical zone centered on the thinnest point, "C" is minimal Corneal thickness, and "D" best spectacle Distance visual acuity. The first 3 parameters (A, B, C) are machine-generated objective measurements that can be used to determine progressive change.The staging system is not limited to a specific commercial entity and can be incorporated in any tomographic imaging system. The ABCD Progression Display graphically displays each parameter and shows when statistical change above measurement noise is reached. This should allow the clinician the ability to diagnose progressive disease at a much earlier stage than was previously possible, with the confidence that earlier intervention could prevent visual loss.

PURPOSE:To determine the impact of corneal crosslinking (CXL) performed over the laser in situ keratomileusis (LASIK) flap using the Standard CXL (S-CXL) protocol or under the flap after flap lift (flap-CXL) on regional corneal stiffness using Brillouin microscopy. SETTING:University of Southern California Keck School of Medicine, Los Angeles, California, and Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA. DESIGN:Laboratory ex vivo experiment. METHODS:After epithelium debridement, LASIK flaps were created on intact fresh porcine eyes with a mechanical microkeratome. Then, S-CXL (riboflavin applied to the corneal surface followed by 3 mW/cm ultraviolet exposure with the flap in place for 30 minutes) or flap-CXL (riboflavin applied to the stromal bed after reflecting the flap followed by the same ultraviolet A exposure with the flap replaced) was performed. Depth profile of stiffness variation and averaged elastic modulus of anterior, middle, and posterior stroma were determined by analyzing Brillouin maps. Each eye served as its own control. RESULTS:The study was performed on 24 fresh porcine eyes. S-CXL had maximal stiffening impact in the anterior most corneal stroma within the LASIK flap (8.40 ± 0.04 GHz), whereas flap-CXL had lower maximal stiffening impact (8.22 ± 0.03 GHz) (P < .001) that occurred 249 ± 34 μm under the corneal surface. S-CXL increased longitudinal modulus by 6.69% (anterior), 0.48% (middle), and -0.91% (posterior) as compared with flap-CXL, which increased longitudinal modulus by 3.43% (anterior, P < .001), 1.23% (middle, P < .1), and -0.78% (posterior, P = .68). CONCLUSIONS:The S-CXL technique generated significantly greater stiffening effect in the anterior cornea than a modified protocol with riboflavin administration under the flap (flap-CXL). Minimal stiffening occurred in the middle or posterior cornea with either protocol.

PURPOSE/OBJECTIVE:Photoactivated chromophore for keratitis cross-linking (PACK-CXL) is used as an adjunct therapy to antibiotic medication in infectious keratitis. This experimental study aimed at quantifying the PACK-CXL efficacy as a function of UV fluence using several bacterial strains and irradiated volumes. METHODS:Six distinct bacterial strains, including standardized strains and clinically isolated strains from patients with keratitis, were analyzed. Bacterial concentrations between 10 and 10 cells/mL were used (simulating small corneal ulcers). Volumes of either 11 μL (≈285 μm stromal thickness) or 40 μL (≈1000 μm stromal thickness) were irradiated within a microtiter plate at different fluences (5.4-27 J/cm) and irradiances (3, 9 and 18 mW/cm). The ratio of bacterial killing (B†) was determined to evaluate the antimicrobial efficacy of PACK-CXL. RESULTS:B† was similar (51 ± 11%) in bacterial concentrations between 10 and 10 per ml. In 11 μL volume, Staphylococcus aureus (SA) 8325-4 ATCC 29213, Bacillus subtilis (BS) 212901, and Pseudomonas aeruginosa (PA) 2016-866624 were most sensitive to PACK-CXL at 5.4 J/cm (on average B† = 49 ± 8%), whereas Klebsiella oxytoca (KO) 2016-86624 (B† = 25%) was least sensitive. When irradiating a larger volume, B† was on average lower in 40 μL (19 ± 18%), compared with 11 μL (45 ± 17%, P < 0.001). By contrast, applying a higher UV fluence increased B† of SA ATCC 29213, from 50% at 5.4 J/cm to 92% at 10.8 J/cm, to 100% at 16.2 J/cm and above. CONCLUSIONS:Applying higher UV fluences substantially increases the bacterial killing rates. Safety limits for clinical application require further investigation.

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.

PURPOSE:Quasi-static optical coherence elastography (OCE) is an emerging technology to investigate corneal biomechanical behavior in situations similar to physiological stress conditions. Herein OCE was applied to evaluate previously inaccessible biomechanical characteristics of human corneal tissue and to study the role of Bowman's layer in corneal biomechanics. METHODS:Human corneal donor buttons (n = 23) were obtained and Descemet's membrane and endothelium were removed. In 11 corneas, Bowman's layer was ablated by a 20 µm stromal excimer laser ablation. Buttons were mounted on an artificial anterior chamber and subjected to a pressure modulation from 10 to 30 mm Hg, and back to 10 mm Hg, in steps of 1 mm Hg. At each step, a spectral-domain optical coherence tomography scan was obtained. Displacements were analyzed by optical flow tracking, and strain over the entire stromal depth was retrieved from the phase gradient of the complex interference signal. RESULTS:During pressure increase, corneal tissue moved upward (486-585 nm/mm Hg) but did not fully recover (Δ= 2.63 to 8.64 µm) after pressure decrease. Vertical corneal strain distribution was negative in the anterior and positive in the posterior cornea, indicating simultaneous corneal compression and expansion, respectively. Bowman's layer caused minor localized differences in corneal strain distribution. CONCLUSIONS:Corneal strain distribution is more complex than previously assumed, with a fundamental difference in mechanical response between the anterior and posterior stroma. Clinically, OCE technology might be used to monitor the progression of corneal ectatic diseases and to determine the success of corneal cross-linking.

BACKGROUND:Middle vault asymmetry is a common reason for retained postoperative deviations. Although minor deformities can be camouflaged with cartilage, soft-tissue materials, or injectable fillers, comprehensive observation of upper lateral cartilage and subsequent topographic classification in major anatomical anomalies will help surgeons better plan their procedures to obtain better symmetry. METHODS:Photographs of 71 randomly selected primary open rhinoplasty patients were analyzed for anatomical presentation of their upper lateral cartilage. Photographs were taken before and after separation of upper lateral cartilage from the septum. Upper lateral cartilage was classified from class I to class V according to the width of the transverse subunits and curvature of the vertical subunits. RESULTS:The authors observed 142 upper lateral cartilages of 71 rhinoplasty patients. Upper lateral cartilage was classified as follows: class I, 53 cases; class II, three cases; class III, 40 cases; class IV, 36 cases; and class V, 10 cases. CONCLUSIONS:Upper lateral cartilage asymmetry is a common occurrence in rhinoplasty, and the upper lateral cartilage itself may be the source of nasal deviation. The middle vault requires special attention, and establishment of a classification system could enable surgeons to devise an effective plan for correction and prevention of retained postoperative nasal deviation.

PURPOSE/OBJECTIVE:To compare the outcomes of accelerated photoactivated chromophore for keratitis corneal cross-linking (PACK-CXL) as an adjunct treatment for bacterial keratitis (PACK-CXL plus standard antibiotic therapy) for patients receiving only standard antibiotic therapy. METHODS:Retrospective cohort study of outcomes of patients with moderate infectious presumed bacterial keratitis (ulcer diameter 2 to 7 mm and stromal depth < 300 µm) were compared before and after initiation of a new treatment protocol of PACK-CXL in addition to standard antibiotic treatment. RESULTS:A total of 70 eyes of 70 patients were included: 39 eyes in the PACK-CXL plus antibiotic (PACK-ABX) group and 31 eyes in the antibiotic only (ABX) control group. The PACK-ABX group showed shorter times to complete reepithelialization (9.3 ± 6.0 vs 16.0 ± 12.7 days, P = .01) and did not require tectonic emergency keratoplasty (0% versus 19.4%, P = .006). The PACK-ABX group also showed a higher percentage of eyes with complete reepithelialization in 6 days or less (46.2% vs 6.5%, P < .001) and a trend for shorter hospitalizations (6.3 ± 5.0 vs 8.5 ± 4.5 days, P = .06). A multivariate analysis controlling for age showed that PACK-ABX treatment remained significantly associated with early ulcer reepithelialization (odds ratio = 0.09, 95% confidence interval = 0.02 to 0.48, P = .005). CONCLUSIONS:This study validates previous findings regarding the use of accelerated PACK-CXL in the treatment of bacterial keratitis. Adding PACK-CXL improved clinical outcomes (reducing healing time) when compared to antibiotics alone. [J Refract Surg. 2020;36(4):258-264.].

BACKGROUND:Facial and cranial asymmetry is common in bilateral vertebrates, particularly human beings. Through years of injecting fillers and performing face-lift operation on patients, we began to observe that more fillers were required on the right side to reach symmetry and also more loose skin and soft tissue was observed on the right side in the majority of patients (Fig. 5). Here, we conducted an analytical study to comprehensively measure human skulls in order to observe and quantify this difference. METHODS:We collected forty-one natural skulls available from five medical schools of Tehran province in Iran. Standard photography was conducted from the front, lateral, and superior views. Measurements and statistics were completed using Image J software (National Institutes of Health) for exact comparison of fixed-point distances on the samples. RESULTS:Comparison of right and left dimensions on the skulls revealed several fixed asymmetries. The most significant differences were measurements around the orbit. The distance between the upper orbit point and zygion (zy), zygion to sub-nasal, and orbital areas were significantly larger on the left side. Measuring the anterior gonion-pogonion distance showed a wider mandibular body on the left side. We did not find any considerable differences between any other left-sided and right-sided skull dimensions. CONCLUSIONS:Asymmetry of the face and body is a general rule in human anatomy, but correlation and consistency of this asymmetry between the left and right sides is a novel finding based on our measurements. Our findings showed that the orbit was significantly bigger in width, height, and surface area on the left side. We also quantified a narrower mandible on the right side. We hope these findings can be translated to aesthetic surgery practice to make the plastic surgeon and patient more familiar with the patient's specific anatomy in order to better predict, plan, and successfully implement aesthetic procedures such as injecting fillers or doing peri-orbital procedures. NO LEVEL ASSIGNED:This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.