Diagnostic Imaging for Retinoblastoma Cancer Staging: Guide for Providing Essential Insights for Ophthalmologists and Oncologists.

Retinoblastoma is the most common cause of all intraocular pediatric malignancies. It is caused by the loss of RB1 tumor suppressor gene function, although some tumors occur due to MYCN oncogene amplification with normal RB1 genes. Nearly half of all retinoblastomas occur due to a hereditary germline RB1 pathogenic variant, most of which manifest with bilateral tumors. This germline RB1 mutation also predisposes to intracranial midline embryonal tumors. Accurate staging of retinoblastoma is crucial in providing optimal vision-, eye-, and life-saving treatment. The AJCC Cancer Staging Manual has undergone significant changes, resulting in a universally accepted system with a multidisciplinary approach for managing retinoblastoma. The authors discuss the role of MRI and other diagnostic imaging techniques in the pretreatment assessment and staging of retinoblastoma. A thorough overview of the prevailing imaging standards and evidence-based perspectives on the benefits and drawbacks of these techniques is provided. Published under a CC BY 4.0 license. Test Your Knowledge questions for this article are available in the supplemental material.

Dysregulated Tear Fluid Nociception-Associated Factors, Corneal Dendritic Cell Density, and Vitamin D Levels in Evaporative Dry Eye.

Purpose: The purpose of this study was to study the status and association among tear-soluble factors, corneal dendritic cell density, vitamin D, and signs and symptoms in dry eye disease (DED). Methods: A total of 33 control subjects and 47 evaporative dry eye patients were included in the study. DED diagnosis and classification was based on the 2017 Report of the Tear Film & Ocular Surface Society International Dry Eye Workshop (TFOS DEWS II). DED workup, including tear film break-up time (TBUT), Schirmer's test I (STI), corneal and conjunctival staining, ocular surface disease index (OSDI) scoring, and in vivo confocal microscopy (to assess corneal dendritic cell density [cDCD] and subbasal nerve plexus [SBNP] features) was performed in the study subjects. Tear fluid using Schirmer's strip and serum were collected from the subjects. Multiplex ELISA or single analyte ELISA was performed to measure 34 tear-soluble factors levels including vitamin D. Results: Significantly higher OSDI discomfort score, lower TBUT, and lower STI were observed in DED patients. cDCD was significantly higher in DED patients. No significant difference was observed in SBNP features. Tear fluid IL-1ß, IL-17A, MMP9, MMP10, MMP9/TIMP ratio, and VEGF-B were significantly higher in DED patients. Significantly lower tear fluid IL-2, IP-10, NPY, VEGF-A, and vitamin D was observed in DED patients. These dysregulated tear factors showed significant associations with DED signs and symptoms. Conclusions: Altered tear fluid soluble factors with potential to modulate nociception exhibited a distinct association with ocular surface discomfort status, TBUT, STI, and cDCD. This implies a functional relationship between the various tear-soluble factors and dry eye pathogenesis, indicating new molecular targets for designing targeted therapies.

In Vivo Prediction of Air-Puff Induced Corneal Deformation Using LASIK, SMILE, and PRK Finite Element Simulations.

Purpose: To simulate deformation amplitude after laser-assisted in situ keratomileusis (LASIK), small incision lenticule extraction (SMILE), and photorefractive keratectomy (PRK) with finite element models. Methods: Finite element simulations of air-puff applanation on LASIK, SMILE, and PRK models were performed on a cohort of normal eyes, which had undergone refractive treatments. Short- and long-term wound healing responses were considered for SMILE and LASIK models based on evidence of microdistortions in Bowman's layer and crimping of collagen fibers. First, inverse simulations were performed to derive the preoperative properties of the cornea. Using these properties and planned refractive treatment, postoperative air-puff deformation amplitude was predicted and compared with the in vivo measurements. Results: The predicted postoperative corneal stiffness parameters agreed very well with in vivo values of SMILE, LASIK, and PRK eyes. Intraclass correlations (ICC) were greatest in PRK eyes (ICC > 0.95). This agreement was lower for peak deformation amplitude and peak deflection amplitude in SMILE and LASIK eyes (ICC < 0.9). In PRK eyes, peak deformation and deflection amplitude predictions were the best relative to in vivo magnitudes. Also, linear correlation (r) between in vivo measurement and predicted biomechanical parameters indicated strong agreement between them (SMILE: r ≥ 0.89, LASIK: r ≥ 0.83, PRK: r ≥ 0.87). Conclusions: The is the first study to present predictive simulations of corneal deformation changes after different procedures. Patient-specific preoperative corneal biomechanical properties and finite element models were a significant determinant of accurate postoperative deformation amplitude prediction.

Allergen-specific exposure associated with high immunoglobulin E and eye rubbing predisposes to progression of keratoconus.

We report two male children with persistent allergic eye disease (AED) and keratoconus (KC). Both presented with symptoms of vernal keratoconjunctivitis and decreased vision. In view of unrelenting AED, serum immunoglobulin E (IgE) quantification and identification of specific allergens were advised. Increased serum IgE levels were observed in both cases. Sunflower and sheep wool were identified as specific allergens for the first and second patient respectively by skin patch test. There was complete resolution of symptoms of AED in both patients following avoidance of causative allergens. However, the progression of KC in both eyes of the first patient and one eye of the second patient was observed. They were advised collagen cross-linking. Elevated serum IgE indicates the presence of systemic allergy. Avoiding implicated allergens help alleviate ocular symptoms. Using serum IgE and identifying specific allergen can guide in the treatment of AED and thus prevent progressive KC due to eye rubbing and resulting inflammation.

Repeatability of a Commercially Available Adaptive Optics Visual Simulator and Aberrometer in Normal and Keratoconic Eyes.

PURPOSE: To evaluate the repeatability of aberration measurement obtained by a Hartmann-Shack aberrometer combined with a visual adaptive optics simulator in normal and keratoconic eyes. METHODS: One hundred fifteen normal eyes and 92 eyes with grade I and II keratoconus, as per the Amsler-Krumeich classification, were included in the study. To evaluate the repeatability, three consecutive measurements of ocular aberrations were obtained by a single operator. Zernike analyses up to the 5th order for a pupil size of 4.5 mm were performed. Statistical analyses included the intraclass correlation coefficient (ICC) and within-subject standard deviation (SD). RESULTS: For intrasession repeatability, the ICC value for sphere and cylinder was 0.94 and 0.93 in normal eyes and 0.98 and 0.97 in keratoconic eyes, respectively. The ICC for root mean square of higher order aberrations (HOARMS) was 0.82 in normal and 0.98 in keratoconic eyes. For 3rd order aberrations (trefoil and coma), the ICC values were greater than 0.87 for normal eyes and greater than 0.92 for keratoconic eyes. The ICC for spherical aberration was 0.92 and 0.90 in normal and keratoconic eyes, respectively. CONCLUSIONS: Visual adaptive optics provided repeatable aberrometry data in both normal and keratoconic eyes. For most of the parameters, the repeatability in eyes with early keratoconus was somewhat better than that for normal eyes. The repeatability of the Zernike terms was acceptable for 3rd order (trefoil and coma) and spherical aberrations. Therefore, visual adaptive optics was a suitable tool to perform repeatable aberrometric measurements. [J Refract Surg. 2017;33(11):769-772.].

Keratoconus Screening Indices and Their Diagnostic Ability to Distinguish Normal From Ectatic Corneas.

PURPOSE: To compare the diagnostic ability of 3 Scheimpflug devices in differentiating normal from ectatic corneas. DESIGN: Comparison of diagnostic instrument accuracy. METHODS: This study included 42 normal, 37 subclinical keratoconic, and 51 keratoconic eyes seen in a tertiary eye care institute. Keratoconus screening indices were evaluated using the Pentacam (Oculus, Wetzlar, Germany), Galilei (Ziemer, Biel, Switzerland), and Sirius (Costruzione Strumenti Oftalmici, Florence, Italy). Sensitivity, specificity, and area under receiver operating characteristic curve (AUC) were calculated. RESULTS: Highest sensitivity (100%) to diagnose keratoconus was seen for 6 parameters on Pentacam and 1 on Galilei. None of the indices in Sirius reached 100% sensitivity. For subclinical keratoconus, the highest sensitivity (100%) was seen for 2 parameters on Pentacam but for none of them on Galilei and Sirius. All parameters were strong enough to differentiate keratoconus (AUC > 0.9). On comparing the best parameters of all 3 machines, the AUC of the Belin/Ambrosio enhanced ectasia total derivation (BAD-D) and the inferior-superior value (ISV) of Pentacam were statistically similar to that of the keratoconus prediction index (KPI) and keratoconus probability (Kprob) of Galilei (P = .27) and 4.5 mm root mean square per unit area (RMS/A) back of Sirius (P = .55). When differentiating subclinical from normal corneas, BAD-D was similar to the surface regularity index (SRI) of Galilei (P = .78) but was significantly greater than the 8 mm RMS/A back of Sirius (P = .002). CONCLUSION: Keratoconus indices measured by all 3 machines can effectively differentiate keratoconus from normal corneas. However, new cutoff values might be needed to differentiate subclinical from normal corneas.