Optimum pinhole size determination in pinhole pupilloplasty for higher-order aberrations.

PURPOSE: To determine optimal pinhole size (OPS) and establish a relationship with visual acuity (VA) and RMS (root mean square) values in cases with higher-order aberrations (HOAs) undergoing pinhole pupilloplasty (PPP). SETTING: Private practice, India. DESIGN: Prospective, interventional study. METHODS: RMS value for 6-mm-diameter optical zone was determined by Scheimpflug imaging (Pentacam). Patients with RMS value >0.3 µm were included. Preoperatively, a hand-held pinhole gauge with varied apertures determined the OPS, and single-pass four-throw technique was used to perform pupilloplasty with Purkinje-1 reflex as a marker for centration. VA with OPS, correlation of RMS values with OPS and pupil size, and Strehl ratio were the main outcome measures. RESULTS: 29 eyes with HOAs were analyzed; all patients chose 1.0 or 1.5 mm as OPS. The mean preoperative and postoperative pupil size was 3.25 ± 0.81 mm and 1.8 ± 0.54 mm ( P = .000), respectively. Postoperative mean pupil size when compared with OPS denoted that 14 eyes had a difference of <0.1 mm, 8 eyes ranged from 0.2 to 0.45 mm, and 7 eyes had ≥0.6 mm (range from 0.6 to 1.8 mm) difference from OPS. Eyes with higher RMS values needed smaller pupil gauge to achieve better VA. Preoperatively, vision with OPS correlated well with preoperative 6-mm RMS HOAs ( r = 0.728; P = .00). Postoperative UDVA correlated well with VA measured with OPS ( r = 0.847; P = .00). The preoperative and postoperative mean Strehl ratio was 0.109 ± 0.07 and 0.195 ± 0.11 ( P = .001), respectively. CONCLUSIONS: Higher RMS values required a smaller pupil to achieve optimum VA. PPP can help achieve pinhole size in accordance with patient's optimum pinhole requirement.

Minimally Invasive Micro Sclerostomy (MIMS) Procedure: A Novel Glaucoma Filtration Procedure.

PRCIS: Intermediate-term results suggest that ab interno Minimally Invasive Micro Sclerostomy (MIMS) stent-less subconjunctival filtration procedure is a promising treatment option for patients with open-angle glaucoma (OAG). PURPOSE: MIMS is a novel ab interno, stent-less, subconjunctival filtration procedure. This study set to investigate the safety, performance, and efficacy of MIMS in OAG patients. METHODS: Prospective, open-label, single arm clinical trial with intrasubject comparisons. Study participants were adults with OAG who were candidates for a filtration procedure. Patients were operated by a single surgeon (A.A.) in Chennai, India. Following mitomycin-C pretreatment, ab interno MIMS procedure was performed alone or combined with phacoemulsification surgery. Procedure-related complications and adverse events were assessed. Primary outcomes: patients (%) achieving an intraocular pressure (IOP) ≥5 mm Hg and ≤18 mm Hg, and an IOP reduction of >20% as compared with baseline, with or without hypotensive medications, with no need for recurrent surgery. RESULTS: Twenty-one phacoemulsification-MIMS and 10 standalone MIMS procedures were performed. Mean age was 63.94±6.33 years. Mean duration of MIMS was 1:58±0:25 (min:s). Scleral tunnels were achieved in all cases. No device malfunctions, intraoperative complications, or serious adverse events were reported. Five (16.12%) patients presented with iris clogging 1 to 24 weeks following procedure. Two were treated with laser and 3 required trabeculectomy. Mean IOP change from baseline at 24 weeks was 47.4% (31.2 to 16.4 mm Hg, P<0.0001, n=23). The mean difference was -14.8 mm Hg (95% confidence interval: -17.6, -11.9) with no statistically significant differences between groups. Qualified success was achieved in 21 (84%), 17 (74%), and 13 (93%) after 12, 24, and 52 weeks, respectively. Complete success was achieved in 17 (68%), 13 (57%), and 8 (57%) after 12, 24, and 52 weeks, respectively. CONCLUSIONS: The interim results suggest that MIMS procedure may be a simple and effective surgical option for early OAG patients requiring target IOP in high teens although iris clogging of incision site is the major concern with this procedure.

Intraocular lens power calculation changes before and after isotonic collagen cross-linking in keratoconus patients.

PURPOSE: To find the intraocular lens (IOL) power calculation changes before and after isotonic collagen cross-linking (CXL) in keratoconus patients. METHODS: : Thirty-five eyes of 25 patients who underwent isotonic CXL were included. The cases included conventional CXL (n = 16), accelerated CXL (n = 7), contact lens-assisted CXL (CACXL) (n = 9), accelerated CACXL (n = 3). All underwent ocular biometry (IOL master), corneal topography (Orbscan II), and simulated keratometry (Orbscan II) preoperatively and 1-year post CXL. Change in best-corrected visual acuity (BCVA), axial length (AL), simulated keratometry (Sim K), anterior chamber depth (ACD), and IOL power were analyzed in the overall data and then grouped based on flattening (Group A) and no flattening (Group B) of Sim K value post CXL procedure. RESULTS: For the overall data, there was no significant change in IOL power (P = 0.05) at the end of 1 year, BCVA showed a significant increase (P < 0.01), and Sim K reading showed a statistically significant flattening (P = 0.001); ACD and AL showed insignificant change. In intergroup comparison, there was no statistically significant change in IOL power. However, in Group A, a significant change in BCVA and Sim K values was observed. In both groups (Group A and Group B), IOL power was found to be negatively correlated with AL and Sim K values. CONCLUSION: Isotonic CXL did not affect IOL power calculation at the end of 1 year. However, significant change in BCVA and sim K reading was noted.

Label-retention expansion microscopy.

Expansion microscopy (ExM) increases the effective resolving power of any microscope by expanding the sample with swellable hydrogel. Since its invention, ExM has been successfully applied to a wide range of cell, tissue, and animal samples. Still, fluorescence signal loss during polymerization and digestion limits molecular-scale imaging using ExM. Here, we report the development of label-retention ExM (LR-ExM) with a set of trifunctional anchors that not only prevent signal loss but also enable high-efficiency labeling using SNAP and CLIP tags. We have demonstrated multicolor LR-ExM for a variety of subcellular structures. Combining LR-ExM with superresolution stochastic optical reconstruction microscopy (STORM), we have achieved molecular resolution in the visualization of polyhedral lattice of clathrin-coated pits in situ.

A ciliopathy complex builds distal appendages to initiate ciliogenesis.

Cells inherit two centrioles, the older of which is uniquely capable of generating a cilium. Using proteomics and superresolved imaging, we identify a module that we term DISCO (distal centriole complex). The DISCO components CEP90, MNR, and OFD1 underlie human ciliopathies. This complex localizes to both distal centrioles and centriolar satellites, proteinaceous granules surrounding centrioles. Cells and mice lacking CEP90 or MNR do not generate cilia, fail to assemble distal appendages, and do not transduce Hedgehog signals. Disrupting the satellite pools does not affect distal appendage assembly, indicating that it is the centriolar populations of MNR and CEP90 that are critical for ciliogenesis. CEP90 recruits the most proximal known distal appendage component, CEP83, to root distal appendage formation, an early step in ciliogenesis. In addition, MNR, but not CEP90, restricts centriolar length by recruiting OFD1. We conclude that DISCO acts at the distal centriole to support ciliogenesis by restraining centriole length and assembling distal appendages, defects in which cause human ciliopathies.

Pinhole pupilloplasty after previous radial keratotomy.

The multiple radial stromal deep corneal incisions placed in radial keratotomy (RK) lead to higher-order aberrations and pose a surgical challenge to performing any further corrective procedure on the cornea because of fear of inducing an incisional dehiscence. A method to perform pinhole pupilloplasty (PPP) in the setting of previous RK is presented. Application of pinhole optics by performing PPP leads to significant improvement in image quality and helps to optimize visual potential in post-RK cases.

Glued intraocular lens in eyes with deficient capsules: retrospective analysis of long-term effects.

PURPOSE: To assess the long-term (6-12 years) results and complications of glued transscleral-fixated intraocular lens (IOL). SETTING: Dr. Agarwal's Eye Center, Chennai, India. DESIGN: Retrospective case series. METHODS: Eyes with glued IOL of more than 5-year follow-up were evaluated. Visual acuity (logarithm of the minimum angle of resolution [logMAR]), IOL tilt, corneal topography, corneal endothelial cell density, intraocular pressure, central corneal thickness, central foveal thickness, and ocular residual astigmatism (ORA) were evaluated. RESULTS: Overall, 91 eyes (63 patients) with mean postoperative 8.2 ± 2.3 years were analyzed. The duration was 10 to 12 years in 31 eyes (34%), 9 years in 14 eyes (15.3%), and 6 to 9 years in 46 eyes (50.5%). No subscleral haptic was visible in 50% eyes. Mild, moderate, and severe grade of haptic visibility was noted in 33.5%, 9.4%, and 7%, respectively. The corrected distance visual acuity (CDVA) was 0.50 ± 0.50 logMAR. Clinically, no tilt was seen in 87 eyes (95.6%), whereas detectable tilt was seen in 4 eyes (4.3%). The optical coherence tomography microtilt was 0.8 ± 1.7 and 0.4 ± 1.2 degrees in 90- and 180-degree axes, respectively. The mean iris vault was 0.45 mm, and the mean ORA was 1.10 ± 1.00 diopter. Complications were glaucoma (7.6%), IOL luxation (4.4%), retinal detachment (3.2%), macular edema (4.3%), corneal decompensation (3.2%), uveitis (2.1%), and uveitis-glaucoma-hyphema syndrome (1%). Haptic reposition (3.2%), retinal detachment surgery (3.2%) keratoplasty (1%), pupilloplasty (2.1%), and IOL explantation (1%) were the second surgeries performed. CONCLUSIONS: Glued IOL has shown good anatomical and functional stability with minimal incidence of vision-threatening complications on long-term.

Pinhole Pupilloplasty for Higher Order Aberrations: Assessment of Visual Quality and Depth of Focus.

PURPOSE: To evaluate visual quality and depth of focus under photopic and mesopic light conditions of patients treated with pinhole pupilloplasty (PPP) for corneal higher order aberrations. METHODS: This was a prospective, noncomparative, interventional series and PPP was performed with a single-pass four-throw procedure in 14 eyes of 14 patients. After PPP, patients were analyzed with the Clinical Trial Suite machine (M & S Technologies, Inc) that offers a standardized method of recording visual quality. The luminance levels of 85 and 3 cd/m2 were set for photopic and mesopic lighting conditions, respectively, and uncorrected and corrected distance visual acuity were recorded for distance (4 m), intermediate (66 cm), and near (44 cm). Low contrast acuity (LCA) at 10% and mesopic contrast sensitivity function (CSF) with glare on and off at four spatial frequencies of 1.5, 3, 6, and 12 cycles per degree (cpd) and defocus curve were assessed. RESULTS: Under photopic and mesopic conditions, a significant difference was observed postoperatively in uncorrected and corrected distance visual acuity for distance, intermediate, and near. The defocus curve demonstrated extended depth of focus that ranged from +1.50 to -2.50 diopters and LCA at 10% demonstrated significant improvement for all cases. For mesopic CSF, a significant improvement was noted at spatial frequencies of 3 and 6 cpd with glare on. With glare off, an improvement was seen at spatial frequencies of 1.5, 3, and 6 cpd, but not at 12 cpd. CONCLUSIONS: Early results demonstrate that PPP provides improved visual quality and extended depth of focus and can be a useful option in cases with higher order aberrations. [J Refract Surg. 2020;36(12):812-819.].

Persistent asymptomatic vitreous cyst with ten years follow-up: A case report.

Asymptomatic free floating vitreous cyst with macular coloboma constantly been stable for 10 years is a rarely reported case. Here, we report a case of 30-year-old male who presented to us with best corrected visual acuity of 6/12 and 6/18 in right and left eye, respectively. On slit-lamp examination anterior segment was normal. His fundus examination showed a solitary free floating cyst in the vitreous in right eye and bilateral macular coloboma. Blood tests for toxoplasmosis and cysticercosis were negative. The patient had no symptoms, so we decided to follow the patient without any treatment.

FIRST-IN-HUMAN CLINICAL STUDY TO INVESTIGATE THE EFFECTIVENESS AND SAFETY OF PARS PLANA VITRECTOMY SURGERY USING A NEW HYPERSONIC TECHNOLOGY.

PURPOSE: Investigate the effective performance and safety of a new hypersonic vitrector technology. METHODS: Postapproval, prospective, single-arm, noncomparative, open-label study at one clinical site in India. INDICATIONS: macular hole (9/20), vitreous hemorrhage (7/20), vitreomacular traction (3/20), and vitreomacular traction with pseudomacular hole (1/20). Safety endpoints included intraoperative and postoperative adverse events. Effective performance endpoints were surgeon-rated effectiveness, range of surgical time, and device settings. Other performance measures were preoperative and postoperative best-corrected visual acuity, slit-lamp and indirect ophthalmoscopy, applanation tonometry, color fundus photography, fundus fluorescein angiography, and spectral domain optical coherence tomography. RESULTS: Core vitreous removal (20/20 subjects), peripheral vitreous removal (18/20), and posterior vitreous detachment induction (13/15) surgeries were successfully completed. Total surgical time was 22.5 minutes to 106 minutes. Serious adverse events through 3 months were 2 device-associated retinal tears and detachment (one intraoperative) and one unrelated postoperative enlargement of macular hole with subretinal fluid. CONCLUSION: This first-in-human study suggests that this new hypersonic vitrector technology is a promising alternative to commercially available guillotine vitrectors. The hypersonic vitrector was effective in core vitreous removal in all cases. Larger-scale studies are required to expand on our initial findings for induction of a posterior vitreous detachment or peripheral vitrectomy.

Densitometry Analysis of Corneal Backscatter After Pre-Descemet Endothelial Keratoplasty for Pseudophakic Bullous Keratopathy.

PURPOSE: To quantify corneal backscattering by densitometry analysis after pre-Descemet endothelial keratoplasty (PDEK). DESIGN: This is a prospective observational case series. METHODS: Setting: Tertiary care hospital. PARTICIPANTS: Postoperative PDEK eyes with best-corrected visual acuity (BCVA) ≥20/40 without comorbidity. OBSERVATION PROCEDURE: Slit-lamp examination, Scheimpflug imaging (Pentacam; Oculus, Wetzlar, Germany), endothelial cell density (cells/mm), and central corneal thickness (Visante; Carl Zeiss AG, Oberkochen, Germany) were performed. Corneal densitometry values for the entire depth of the cornea were compared between post-PDEK eyes and fellow eyes (non-PDEK). MAIN OUTCOME MEASURES: Mean densitometry (grayscale units, GSUs) of the anterior, posterior, central, total depth and concentric zones (0-2, 2-6, 6-10, and 10-12 mm) of the cornea. RESULTS: Overall, 35 eyes (21 PDEK eyes and 14 control eyes) were evaluated. The mean total densitometry values in the anterior, central, and posterior corneas were 40.7 ± 7.6 GSU, 25.3 ± 4.8 GSU, and 20.9 ± 3.4 GSU, respectively. On inter-zone comparison between central and peripheral cornea, there was a statistically significant difference (P < 0.05) between 0 to 2 mm and 6 to 12 mm zones. There was no correlation between endothelial cell density and central corneal thickness with densitometry. However, there was a significant correlation of BCVA with corneal densitometry in 0 to 2 mm (r = 0.519, P = 0.016) and 6 to 2 mm (r = 0.556, P = 0.009) zones. In eyes with BCVA 20/20, there was no significant difference between PDEK and control eyes in the total corneal densitometry in the entire depth of the cornea (P = 0.662). CONCLUSIONS: Clinically clear corneas with visual acuity 20/20 showed no difference in the total corneal densitometry as compared to their fellow eye. Corneal backscatter was higher in the anterior cornea and in the central 0 to 6 mm zone.

Cilia-based peptidergic signaling.

Peptide-based intercellular communication is a ubiquitous and ancient process that predates evolution of the nervous system. Cilia are essential signaling centers that both receive information from the environment and secrete bioactive extracellular vesicles (ectosomes). However, the nature of these secreted signals and their biological functions remain poorly understood. Here, we report the developmentally regulated release of the peptide amidating enzyme, peptidylglycine α-amidating monooxygenase (PAM), and the presence of peptidergic signaling machinery (including propeptide precursors, subtilisin-like prohormone convertases, amidated products, and receptors) in ciliary ectosomes from the green alga Chlamydomonas. One identified amidated PAM product serves as a chemoattractant for mating-type minus gametes but repels plus gametes. Thus, cilia provide a previously unappreciated route for the secretion of amidated signaling peptides. Our study in Chlamydomonas and the presence of PAM in mammalian cilia suggest that ciliary ectosome-mediated peptidergic signaling dates to the early eukaryotes and plays key roles in metazoan physiology.

Application of Purkinje images for pinhole pupilloplasty and relevance to chord length mu.

PURPOSE: To evaluate the results of pinhole pupilloplasty in cases with high astigmatism and higher-order aberrations (HOAs). SETTING: Dr. Agarwal's Eye Hospital & Research Centre, Chennai. DESIGN: Case series. METHODS: Pinhole pupilloplasty was performed based on the Purkinje 1 (P1) images formed from the light source of a Lumera surgical microscope; the images served as a reference marker for centration. A single-pass 4-throw technique was used to achieve a pinhole pupil. The preoperative and postoperative pupil diameter, uncorrected (UDVA) and corrected (CDVA) distance visual acuities, simulated keratometry (K), and chord length mu (µ) were assessed, the latter using a Pentacam rotating Scheimpflug camera. RESULTS: Pinhole pupilloplasty was performed in 8 eyes (8 patients). There was a statistically significant reduction in the mean horizontal and vertical pupil diameters and in the mean pupil diameter from preoperatively to postoperatively (both P < .001). Although the improvement in UDVA was statistically significant (P < .001), the change in CDVA was not. The mean simulated K and mean chord length µ values were significantly lower postoperatively (P = .024 and P < .001, respectively). The reduction in pupil size was more apparent than the reduction in chord length µ. The correlation between the change in chord length µ and the change in pupil size was not significant (r = -0.067, P = .874). The pupil was well centered on the P1 images. No major adverse events or complications occurred postoperatively. CONCLUSION: Postoperative results showed a correlation between the improvement in visual acuity and the decrease in pupil size and chord length µ.

Ciliary and cytoskeletal functions of an ancient monooxygenase essential for bioactive amidated peptide synthesis.

Many secreted peptides used for cell-cell communication require conversion of a C-terminal glycine to an amide for bioactivity. This reaction is catalyzed only by the integral membrane protein peptidylglycine α-amidating monooxygenase (PAM). PAM has been highly conserved and is found throughout the metazoa; PAM-like sequences are also present in choanoflagellates, filastereans, unicellular and colonial chlorophyte green algae, dinoflagellates and haptophytes. Recent studies have revealed that in addition to playing a key role in peptidergic signaling, PAM also regulates ciliogenesis in vertebrates, planaria and chlorophyte algae, and is required for the stability of actin-based microvilli. Here we briefly introduce the basic principles involved in ciliogenesis, the sequential reactions catalyzed by PAM and the trafficking of PAM through the secretory and endocytic pathways. We then discuss the multi-faceted roles this enzyme plays in the formation and maintenance of cytoskeleton-based cellular protrusions and propose models for how PAM protein and amidating activity might contribute to ciliogenesis. Finally, we consider why some ciliated organisms lack PAM, and discuss the potential ramifications of ciliary localized PAM for the endocrine features commonly observed in patients with ciliopathies.

Structural insights on druggable hotspots in CD147: A bull's eye view.

CD147/Basigin/EMMPRIN (Extracellular Matrix Metalloproteinase inducer) is a single pass type1 transmembrane protein playing a central role in developmental process, wound healing, nutrient transport, inflammation, arthritis and also in microbial pathologies. It is also found to be a potent stimulator of MMP (matrix metalloproteinases) and has been considered as a prognostic marker in cancer. Dysregulation of CD147 is reported in several types of cancer. It activates cell proliferation, invasion, metastasis and inhibits tumor cell apoptosis under hypoxic condition. Thus, CD147 serves as a hub protein in cancer, as it is involved in several homophilic and heterophilic cellular interactions spanning the major hallmarks of cancer. Targeting these interactions is considered to be an efficient therapeutic modality in cancerous conditions. Hence, by this review we intend to collate the structure-function relationships of CD147, with an exclusive thrust on potential druggable hotspots based on its intra and inter molecular interactions.

Pinhole pupilloplasty: Small-aperture optics for higher-order corneal aberrations.

This technique of performing pinhole pupilloplasty helps filter the straylight from the periphery of the cornea in cases with higher-order corneal aberrations. The pinhole effect blocks distorted and unfocused light rays and isolates more focused central and paracentral rays through the central aperture, thereby reducing aberrations of the optical system as a whole and enhancing visual acuity and its image quality.

Epiretinal membrane profile on spectral domain optical coherence tomography in patients with uveitis.

PURPOSE: To study the epiretinal membrane (ERM) profile on the spectral-domain optical coherence tomography (SDOCT) in eyes with uveitis. METHODS: In this prospective observational study, macula of uveitic eyes were evaluated by SDOCT (Cirrus, model 5000) for ERM. ERM was quantified (in microns) and were followed up along with the best-corrected visual acuity (BCVA) and treatment profile for 1 year. ERM morphology (focal, global, or mixed) and characteristics (thickness at fovea, maximum thickness, and location of maximum thickness in relation to fovea) were documented. Changes in altered foveal contour, cystoid macular edema (CME), and central foveal thickness were also noted. BCVA was noted when the inflammation subsided and it was correlated to specific ERM characteristics. SDOCT characteristics were compared in three treatment groups (no oral steroids, oral steroids with, and without immunomodulators). RESULTS: Thirty-four eyes of 25 patients were evaluated. Mean logMAR BCVA decreased from 0.25 to 0.35 (P = 0.005). Foveal involvement with ERM (P = 0.011), lost foveal contour (P = 0.043), and ellipsoid layer disruption (P = 0.017) were associated significantly with reduced BCVA. Focal attachment of ERM was more commonly associated with CME (P = 0.03). Median ERM thickness showed significant increase (P < 0.001). Significant ERM progression from parafoveal to foveal (P = 0.02), significant progression of the thickest area of ERM closer to fovea (P = 0.0006) indicated a strong tendency of foveal involvement and this was correlated with worse BCVA (P = 0.009, r = -0.44) Oral steroids/immunomodulators showed no significant benefit on ERM progression. CONCLUSION: ERM progression in uveitis has a tendency to involve the fovea and is associated with significant vision loss, particularly in foveal ERM, focal attachment, and IS-OS disruption. Oral steroids and immunomodulators have no role in halting progression.

Iris and knot configuration after Single Pass Four Throw (SFT) pupilloplasty as imaged by the spectral-domain optical coherence tomography.

PURPOSE: To analyze the morphological changes in the iris-knot complex configuration using spectral-domain optical coherence tomography (SD-OCT) following the single pass four throw (SFT) pupilloplasty. METHODS: In this retrospective case series, eyes with SFT pupilloplasty were examined by SD-OCT (Optovue). Iris morphology compared to the normal iris, presence of specific patterns (single hump, double humps, peaks and valleys, tethering), prolene suture, knot complex (length and orientation), and intraocular lens (IOL) vault were evaluated. RESULTS: Overall, 41 knots of 26 patients with a mean time duration of 3.1 ± 2 months from surgery were analyzed. Iris configurations seen were single hump (n = 28, 63.8%), double humps (n = 7, 17%), loop (n = 2, 4.8%), flat (n = 3, 7.3%), and mulberry (n = 1, 2.4%). The mean length and the height of the knot complex was 784.1 ± 433.7 µm and 317.7 ± 110.4 µm, respectively. Knot positions were at 3 clock hours in 9 eyes (21.9%), 9 in 8 eyes (19.5%), and others in 24 eyes (58.5%). Cut end of the prolene suture was detectable in 26 eyes (63.4%) as hyper-reflective line, and the mean cut length was 465.8 ± 321.1 µm. The suture was predominantly vertically oriented (80.6%) to the iris with a mean distance of 3.6 ± 0.3 mm (2.6-4 mm) away from corneal endothelium. The mean distance from the knot complex and the IOL was 289.2 ± 146 µm and the mean anterior chamber depth was 4.1 ± 0.1 mm. CONCLUSION: A significant change in iris configuration was noted after SFT pupilloplasty, and vertically oriented retained prolene suture was predominant with good endothelial vault.