Myo/Nog Cells: Targets for Preventing the Accumulation of Skeletal Muscle-Like Cells in the Human Lens

Posterior capsule opacification (PCO) is a vision impairing condition that arises in some patients following cataract surgery. The fibrotic form of PCO is caused by myofibroblasts that may emerge in the lens years after surgery. In the chick embryo lens, myofibroblasts are derived from Myo/Nog cells that are identified by their expression of the skeletal muscle specific transcription factor MyoD, the bone morphogenetic protein inhibitor Noggin, and the epitope recognized by the G8 monoclonal antibody. The goal of this study was to test the hypothesis that depletion of Myo/Nog cells will prevent the accumulation of myofibroblasts in human lens tissue. Myo/Nog cells were present in anterior, equatorial and bow regions of the human lens, cornea and ciliary processes. In anterior lens tissue removed by capsulorhexis, Myo/Nog cells had synthesized myofibroblast and skeletal muscle proteins, including vimentin, MyoD and sarcomeric myosin. Alpha smooth muscle actin (a-SMA) was detected in a subpopulation of Myo/Nog cells. Areas of the capsule denuded of epithelial cells were surrounded by Myo/Nog cells. Some of these cell free areas contained a wrinkle in the capsule. Depletion of Myo/Nog cells eliminated cells expressing skeletal muscle proteins in 5-day cultures but did not affect cells immunoreactive for beaded filament proteins that accumulate in differentiating lens epithelial cells. Transforming growth factor-betas 1 and 2 that mediate an epithelial-mesenchymal transition, did not induce the expression of skeletal muscle proteins in lens cells following Myo/Nog cell depletion. This study demonstrates that Myo/Nog cells in anterior lens tissue removed from cataract patients have undergone a partial differentiation to skeletal muscle. Myo/Nog cells appear to be the source of skeletal muscle-like cells in explants of human lens tissue. Targeting Myo/Nog cells with the G8 antibody during cataract surgery may reduce the incidence of PCO

Outcomes of four-point suture fixated and two-point sutureless posterior chamber IOLs combined with pars plana vitrectomy

Background While each scleral fixation method has its own advantages, there is a lack of strong evidence to suggest a superior technique. Advances in cataract surgery expand patient eligibility for successful cataract extraction, benefitting a growing population of pseudophakic patients. However, implantation of secondary intraocular lens (IOL) with compromised anterior or posterior capsule is a more challenging task. Each method of scleral fixation has its own advantages and none of them has strong evidence to be superior. This paper describes postsurgical outcomes of two scleral intraocular(IOL) fixation techniques combined with pars plana vitrectomy(PPV) from a single tertiary referral eye center. Methods Patients underwent PPV and IOL implantation with either four-point sutured scleral fixation (Akreos AO60(AK); n = 24) or two-point sutureless flanged intrascleral fixation (CT Lucia(CTL); n = 7). Reports include IOL and sclerotomy placement, fixation techniques, and IOL model. Results Thirty-one eyes of thirty patients were analyzed. Average change in vision from baseline measurement was LogMAR − 0.68 ± 0.66 and − 0.90 ± 0.63 for AK and CTL groups, respectively. Average postoperative refractive error was − 0.3 ± 1.03 D (AK) and 0.4 ± 0.60 D (CTL). No opacification cases of Akreos lens were found in this study with the longest follow up of 53 months. Conclusions Both methods of implantation (sutured and sutureless) could provide good visual and refractive outcomes. Minimal complication rates were reported despite including patients with multiple comorbidities, making both techniques an attractive choice for secondary IOL implantation

Evaluating techniques to improve visual performance with and assessment of premium intraocular lenses

Premium Intraocular Lenses (IOLs) such as toric IOLs, multifocal IOLs (MIOLs) and accommodating IOLs (AIOLs) can provide better refractive and visual outcomes compared to standard monofocal designs, leading to greater levels of post-operative spectacle independence. The principal theme of this thesis relates to the development of new assessment techniques that can help to improve future premium IOL design. IOLs designed to correct astigmatism form the focus of the first part of the thesis. A novel toric IOL design was devised to decrease the effect of toric rotation on patient visual acuity, but found to have neither a beneficial or detrimental impact on visual acuity retention. IOL tilt, like rotation, may curtail visual performance; however current IOL tilt measurement techniques require the use of specialist equipment not readily available in most ophthalmological clinics. Thus a new idea that applied Pythagoras’s theory to digital images of IOL optic symmetricality in order to calculate tilt was proposed, and shown to be both accurate and highly repeatable. A literature review revealed little information on the relationship between IOL tilt, decentration and rotation and so this was examined. A poor correlation between these factors was found, indicating they occur independently of each other. Next, presbyopia correcting IOLs were investigated. The light distribution of different MIOLs and an AIOL was assessed using perimetry, to establish whether this could be used to inform optimal IOL design. Anticipated differences in threshold sensitivity between IOLs were not however found, thus perimetry was concluded to be ineffective in mapping retinal projection of blur. The observed difference between subjective and objective measures of accommodation, arising from the influence of pseudoaccommodative factors, was explored next to establish how much additional objective power would be required to restore the eye’s focus with AIOLs. Blur tolerance was found to be the key contributor to the ocular depth of focus, with an approximate dioptric influence of 0.60D. Our understanding of MIOLs may be limited by the need for subjective defocus curves, which are lengthy and do not permit important additional measures to be undertaken. The use of aberrometry to provide faster objective defocus curves was examined. Although subjective and objective measures related well, the peaks of the MIOL defocus curve profile were not evident with objective prediction of acuity, indicating a need for further refinement of visual quality metrics based on ocular aberrations. The experiments detailed in the thesis evaluate methods to improve visual performance with toric IOLs. They also investigate new techniques to allow more rapid post-operative assessment of premium IOLs, which could allow greater insights to be obtained into several aspects of visual quality, in order to optimise future IOL design and ultimately enhance patient satisfaction

Objective and subjective evaluation of dysphotopsia in normal and post-operative eyes

The principle theme of this thesis is the measurement of dysphotopsia, a common complaint in both the ageing population and after cataract or refractive surgery. Despite the availability of multiple objective and subjective methods to measure dysphotopsia, no single method is in common use, nor are photic effects commonly measured prior to cataract or refractives urgery. In this thesis, objective measures are taken using the Aston halometer and C-Quant, whilst subjective complaints are graded using simulated images. Whilst many previously published studies have reported monocular halometry results, an early study in the thesis found monocular halo areas to be approximately 30 % larger (P < 0.001) than the binocular area, indicating the effect of binocular summation on objective measures of halo area. The thesis investigates the link between objective measures and subjective complaints of dysphotopsia. Subjective complaints were not linked to binocular halo area (P = 0.478), monocular halo area (P = 0.896) or C-Quant straylight values(P = 0.128). Halometry and C-Quant also showed no relationship (P = 0.229). The results highlight the difficulties in being able to predict the potential subjective complaints a patient may experience from objective measures alone. However, a weak correlation was found between binocular halo area and subjective night halo complaints (rs = 0.330, rs2 = 0.109, P < 0.001), which may be due to the fact that halo area assessed would relate directly to the night halo image on the photographic images of photic phenomena (PIPP) plates. Binocular and monocular halo areas both increased with age (rs = 0.449, rs2 = 0.202, P < 0.001 and rs = 0.403, rs2 = 0.162, P < 0.001, respectively) in healthy eyes (n = 141, age range 18 – 82 years). Retinal straylight values also increased significantly with age (rs = 0.457, rs2 = 0.209, P < 0.001), as did subjective grading (rs = 0.314, rs2 = 0.099, P < 0.001). The results indicate a significant age-related increase in dysphotopsia, even in healthy eyes, which is attributed to media changes over time. Due to the effects of a bright light source on the pupil size, and the issue of senile miosis, this programme of research considered, for the first time, whether pupil size had an effect on the size of the halo area measured with halometry. No significant difference in halo area with various simulated pupil sizes (4.5, 6.0 and 7.5 mm) was detected (χ2(3) = 7.56, P = 0.056). The Aston halometer is therefore a robust way to evaluate dysphotopsia without measuring or controlling pupil size. A longitudinal study tracked photic effects in individuals for a year after laser-assisted in situ keratomileusis, and another measured dysphotopsia pre- and up to a year post-cataract surgery. Subjective complaints resolved by 3 months post-refractive surgery, objective halo area took 6 months to resolve post cataract surgery and up to 12 months post-corneal refractive surgery. A glare effect ratio was calculated for binocular halometry (median = 1.28; IQR 0.75 – 2.15) and retinal straylight (median = 5.63; IQR 2.72 – 7.97). The glare effect ratio is independent of age, and it is suggested that the glare effect ratio could be used to identify individuals most at risk of significant subjective complaints of dysphotopsia following procedures such as corneal refractive surgery

CLINICAL OUTCOMES POST-IMPLANTATION OF MULTIFOCAL AND TORIC INTRAOCULAR LENSES

In order to increase spectacle independence following cataract surgery and intraocular lens (IOL) implantation; correction of spherical refractive error, astigmatic error and presbyopia should all be given careful consideration. There are many premium IOLs, including multifocal intraocular lenses (MIOLs) and toric intraocular lenses (TIOLs), available to surgeons. In order to select the appropriate IOL to meet a patient’s lifestyle and expectations, clinicians must fully understand the characteristics of MIOL and TIOL designs. To date, there remain unanswered questions pertaining to MIOLs and TIOLs and by rigorous comparison of such lenses, this thesis aims to address some of the gaps in the current literature. This thesis aims to evaluate a robust protocol for investigating clinical outcomes in MIOLs that would allow for comparison between future studies. This methodology was used in a randomised control trial and a cohort study. Included in this protocol is the detailed analysis of defocus profiles. This thesis investigates polynomial curve fitting to establish the most suitable curve and curve fitting method for use in future analysis of MIOLs with detailed defocus metrics. Defocus curves can highlight the differences in optical performance in MIOLs of differing addition powers, however, to add further complexity, previous literature has highlighted that addition power can vary individual to individual based on their ocular anatomy. Thus, investigation of an easily accessible clinical method to predict the likely achieved addition power post-implantation was performed. A randomised intra-patient contralateral eye study assessed refractive outcomes and rotational stability in TIOLs. In addition, the performance of the corresponding manufacturer’s calculators was evaluated in regard to refractive predictability and appropriate TIOL selection. This thesis highlights the clinical features of modern MIOL and TIOL designs, demonstrating both the benefits and challenges incurred following implantation.University of Plymout

Patient-Perceived and Laboratory-Measured Halos Associated with Diffractive Bifocal and Trifocal Intraocular Lenses

Purpose: To examine and assess the halos generated in distance vision by multifocal intraocular lenses (IOLs) using both in vitro objective and in vivo subjective methods. Setting: The objective method was carried out in the optics laboratory of the Applied Optics and Image Processing Group (Universitat Politècnica de Catalunya -Barcelona). The psychophysical and subjective methods were carried out in the Instituto de Oftalmología Avanzada Madrid Innova Ocular. Design: Optical bench results and prospective evaluation of consecutive cases. Methods: The IOLs examined were TECNIS®one-piece bifocals with addition powers of +4.00 D, +3.25 D, and +2.75 D and the trifocals AT-LISA-tri® and FineVision®. In the objective assessment, we examined halos around the far focus images of a pinhole formed by each IOL in an optical bench. For the in vivo study, we recruited 100 patients who had been bilaterally implanted one month earlier with the IOLs under study. Participants were subjected to psychophysical halometry (Halo v1.0) on the eye with better, distance-corrected, visual acuity and were required to subjectively grade halos by responding to the question “How much do halos bother you?” Results: The objective method revealed that the halo size increased with addition power and that the two trifocals gave rise to a double-halo pattern. Scores in the halometry also indicated a direct relationship between the halo size and addition power. The subjective results indicated fewer complaints about halos associated with the trifocal than bifocal IOLs. Conclusions: The addition power of the tested IOLs affected both laboratory-measured and patient-perceived halos. Trifocal lenses generated fewer complaints about halos. Precise: Multifocal intraocular lenses (MIOLs) give rise to halos observed by patients under conditions of dim lighting. This study compares laboratory characterized halos generated by five MIOLs with patient-perceived halos.Postprint (author's final draft

Vision Correction and Eye Surgery

This book focuses on the current approaches in the medical and surgical treatment of the most diffuse and important ocular diseases. It reports the latest developments in surgery (anterior segment surgery, posterior pole surgery, etc.) for various types of ocular disease, including glaucoma, corneal diseases, and vitreoretinal disease. the latest developments in the surgical field of ocular disease from the anterior segment to the posterior pole going through the main ocular disease (cataract surgery in normal and/or complicated conditions, glaucoma, corneal diseases, and vitreoretinal disease), with the latest developments in the treatment of ocular disease that enable improved surgical outcomes and fewer complications