Novel Technique of Transepithelial Corneal Cross-Linking Using Iontophoresis in Progressive Keratoconus

In this work, the authors presented the techniques and the preliminary results at 6 months of a randomized controlled trial (NCT02117999) comparing a novel transepithelial corneal cross-linking protocol using iontophoresis with the Dresden protocol for the treatment of progressive keratoconus. At 6months, there was a significant average improvement with an average flattening of themaximum simulated keratometry reading of 0.72\ub11.20D(P = 0.01); in addition, corrected distance visual acuity improved significantly (P = 0.08) and spherical equivalent refraction was significantly lessmyopic (P = 0.02) 6months a\u17fter transepithelial corneal cross-linkingwith iontophoresis. The novel protocol using iontophoresis showed comparable resultswith standard corneal cross-linking to halt progression of keratoconus during 6-month follow-up. Investigation of the long-term RCT outcomes are ongoing to verify the efficacy of this transepithelial corneal cross-linking protocol and to determine if it may be comparable with standard corneal cross-linking in themanagement of progressive keratoconus

Innovative Diagnostic Tools for Ophthalmology in Low-Income Countries

Globally, there are almost 300 million people blind and visually impaired and over 90% live developing countries. The gross disparity in access to ophthalmologists limits the ability to accurately diagnose potentially blinding conditions like cataract, glaucoma, trachoma, uncorrected refractive error and limits timely initiation of medical and surgical treatment. Since 85% of blindness is preventable, bridging this chasm for care is even more critical in preventing needless blindness. Many low-income countries must rely on community health workers, physician assistants, and cataract surgeons for primary eye care. Ophthalmology in low-income countries (LIC) is further challenging due to complexities brought from tropical climates, frail electric grids, poor road and water infrastructure, limited diagnostic capability and limited treatment options. Vision 2020 set the goal of eliminating preventable blindness by 2020 despite formidable obstacles. Innovative technologies are emerging to test visual acuity, correct refractive error quickly and inexpensively, capture retinal images with portable tools, train cataract surgeons using simulators, capitalize on mHealth, access ophthalmic information remotely. These advancements are allowing nonspecialized ophthalmic practitioners to provide low-cost, high impact eye care in resource-limited regions around the world

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

Aspheric intraocular lens in cataract surgery

This thesis, by prior publication, encompasses an overview and critical analysis of 6 publications on aspheric intraocular lenses (IOLs) carried out at St. Thomas’ Hospital, Guy’s & St. Thomas’ NHS Foundation Trust, London between 2006 2012. The focus is on two areas: the visual and optical performance of aspheric IOLs with different values of asphericity, and their effect on posterior capsule opacification (PCO). Chapter 1 describes the history of IOLs and the evolution of aspheric IOLs. It also presents relevant optical concepts. The three publications presented in Chapter 2 compare aspheric IOLs with spherical IOLs. The results come from two prospective, randomised, fellow-eye comparison studies: one comparing a spherical Alcon AcrySof SN60AT versus the aspheric Alcon AcrySof SN60WF (with negative asphericity), which partially corrects corneal spherical aberrations, and the other comparing the Zeiss AcriSmart 36A (with negative asphericity), which partially corrects corneal spherical aberrations, and the Bausch & Lomb Akreos MI60 (with neutral asphericity), which has zero spherical aberration. The third publication reports changes in vertical coma after implantation of all the above lenses and additionally includes data on two spherical IOLs from a previous study by our group (the three piece Alcon MA60AC IOL and the plate haptic HumanOptic MC611MI IOL). For this study, the data were divided according to their asphericity and not design. To avoid confounding from aberrometric differences due to astigmatism and surgical techniques, standard incision sizes of 2.75 mm and 2.4 mm were used in the two felloweye, randomised studies and a single surgeon performed all the surgeries using same incision size for each study. Results demonstrated that the aspheric IOLs significantly reduced spherical aberration, improved mesopic contrast sensitivity and reduced depth-of-focus. Asphericity differences up to 20 μm were not associated with depth-of-focus and the degree of asphericity was not associated with best-corrected distance visual acuity. The vertical coma varied within IOL groups of the same asphericity but there was no statistically significant difference between the two spherical IOLs (AcrySof SN60AT and AcrySof MA60AC). Further critical analysis of our data already published showed no statistically significant difference in mean vertical coma between the AcrySof MA60AC (-0.060 ± 0.211μm) with that of Akreos MI60 (- 0.042 ± 0.148μm) (p=0.70) and AcriSmart 36A (-0.034 ± 0.141μm) (p=0.58) even though the AcrySof MA60AC, Akreos MI60 and AcriSmart 36A IOLs had different asphericity. This may be due to the difference in the IOL designs, decentration and difference in the sample sizes between groups. Chapter 3 discusses the findings of three publications related to posterior capsule opacification (PCO). The first publication is an in vitro study assessing posterior optic square edges of various commercially available spherical and aspherical IOLs. Results demonstrated hydrophilic IOLs had less sharp square edges compared to hydrophobic IOLs. Although these in vitro results are potentially significant, there are currently no in vivo studies on the lenses used to compare our results with. The other two publications are based on the PCO outcomes from the prospective, randomised, fellow-eye studies described above. There was no difference in the PCO rates between hydrophobic spherical AcrySof SN60AT and aspheric AcrySof SN60WF IOLs of the same design at 2 years. In contrast, we found a significant increase in the PCO with both the hydrophilic acrylic AcriSmart 36A and Akreos MI60 IOLs (one with negative asphericity and one with neutral asphericity). Variation in asphericity did not appear to be an important factor contributing to the PCO but it was apparent that the edge design and material of the IOL were important with regards to the PCO formation. Finally, since these publications, some of manufacturers have changed their IOL models and today a majority of the IOLs have are aspheric and have a sharp edge profile. The overall, benefit of using aspheric IOLs seems to be limited as it is dependent on the natural pupil size

The simulated ocular surgery (SOS) trials: randomised-controlled trials comparing intense simulation-based surgical edication for cataract and glaucoma surgery to conventional training alone in East and Southern Africa

Cataract remains the most common cause of blindness globally, and glaucoma is the third after uncorrected refractive error. Surgical management remains a priority, yet surgical training of ophthalmologists continues in the outdated apprentice model. Simulation-based surgical education is yet to be tested to the level of a randomised-controlled trial in ophthalmology. We designed two separate and independent multi-centre multi-country investigator-masked randomised controlled educational-intervention parallel group efficacy trials. Post-graduate doctors in ophthalmology training programmes at collaborating institutions in five East and Southern African countries were assessed for eligibility for inclusion (not having performed the procedure as primary surgeon) into either the OLIMPICS (ophthalmic learning and improvement initiative in cataract surgery) or GLASS (glaucoma simulated surgery) trials. Fifty-one surgical trainees were recruited into the GLASS trial, and 50 into the OLIMPICS trial. Surgical competency was assessed by video recordings, which were double marked by independent experts who were masked to group assignment and timing of the assessment. The intervention was an intense simulation-based cataract or glaucoma surgical training course over 5 days. Primary outcome measure was surgical competency at three-months assessed with validated simulated surgical competency assessment rubrics, the Sim-OSSCARs (ophthalmic simulation surgical competency assessment rubric), for both trials. The trials were registered in March 2017 on the Pan-African Clinical Trial Registry (PACTR201803002159198) and are currently closed to recruitment. Baseline characteristics of age, sex, year of training, baseline knowledge and competency scores were balanced between both arms, for both trials. In total 1,361 surgical videos from across different time-points were independently graded by two separate graders in both trials. In the OLIMPICS trial, 50 participants were recruited between November 2017 and May 2018 and 49 included in the final intention-to-treat analysis with one dropout from the control group. Intervention group participants increased mean simulated surgical competence scores from a baseline of 10.8 of 40 points (27.0%) to 33.7 (84.2%) at 3-months after the training intervention, an increase of 212%. Control group participants’ mean baseline scores were 12.8 (31.9%) and 3-month scores 17.9 (44.7%). We found strong evidence (linear regression p<0.0001) that those in the intervention arm were estimated to have higher scores at three months than those in the control arm, after adjusting for baseline score. Among individuals with the same baseline score, those who received the training were estimated to have scores 16.6 points higher (95%CI 14.5 to 18.8) at three months, compared to those who had not received the training. Intervention participants performed a mean of 22 cataract surgeries as primary surgeon in the one year following the training intervention, compared to 9 by control participants (Poisson regression p<0.0001). Surgical complications were reported for the one year period, and posterior capsule rupture (PCR) rates were 7.4% for the intervention group compared to 26.2% for controls (p<0.0001). Confidence rating scores were assessed using a ten-point Likert scale anchored at 1=’not confident at all’, and 10=’very confident’. Confidence as cataract surgeons increased from 2.2 (of 10) to 6.3 at three-months in the intervention group, compared to 3.4 at baseline to 4.2 for the control group. Among individuals with the same baseline confidence score, those receiving the training were estimated to have scores 2.7 points higher (95%CI 1.6 to 3.7) (p<0.001). In the GLASS trial, 53 trainee ophthalmologists were assessed for eligibility, and 51 were enrolled and randomised. Forty-nine participants were included in the final intention-to-treat analysis: 23 intervention and 26 control, following two drop outs from the intervention group. Baseline surgical competency scores for intervention were a mean of 9.1/40 (22.6%) [median 7.3, IQR 5.4-12.1]; and for control: 8.7/40 (21.8%) [median 8.2, IQR 6.3-12.0] participants. Mean Sim-OSSCAR scores at three-months were 30.4 (76.1%) [median 30.3 IQR 27.8-33.5] and 9.8 (24.4%) [median 9.2 IQR 7.5-11.7] for intervention and control groups respectively. We found strong evidence (linear regression p<0.0001) that those in the intervention arm were estimated to have higher scores at three months than those in the control arm, after adjusting for baseline score as a fixed effect. Among individuals with the same baseline score, those who received the training were estimated to have scores 20.5 points (of 40) higher (95%CI 18.4 to 22.6) at three months, compared to those who had not received the training (linear regression p<0.0001). Baseline mean self-reported confidence in glaucoma surgical skills was 3.0/10 for intervention and 3.2 for control participants. This increased to mean 6.4 and 3.7 at three months respectively (p=0.002). Trainee participants in the intervention group performed a mean of 3.1 live surgical trabeculectomies as primary surgeon over one year following training (median 2, range 0-15, IQR 0-4). Over the same period (and before their simulation training) the control group performed a mean of 0.15 (only one of the 26 control participants performed any glaucoma surgery, compared to 14 of the 23 intervention participants). These are the first multi-centre ophthalmic simulation surgery educational-intervention randomised controlled trials ever conducted. Intense simulation training affords a rapid and sustained increase in surgical competence, confidence as a surgeon, and impacts the number of live surgeries performed. Simulation education in cataract surgery affords a striking benefit in terms of patient safety

Ophthalmic Optics and Visual Function

Exploring quality of vision is one of the most important issues in modern ophthalmology, and research into ophthalmic optics and visual function is essential for making progress in this field. The present Special Issue aims to enlighten readers about the broad range of clinical research in the field of ophthalmic optics and visual function, mainly related to the anterior segment and myopia control. Submissions of original research articles were welcomed that highlight innovative findings with the potential to enhance the clinical capabilities of diagnosing and monitoring ophthalmic conditions and treatments especially of the anterior segment. Review articles of high interest were also considered for publication

Generation of Artificial Image and Video Data for Medical Deep Learning Applications

Neuronale Netze haben in den letzten Jahren erstaunliche Ergebnisse bei der Erkennung von Ereignissen im Bereich der medizinischen Bild- und Videoanalyse erzielt. Dabei stellte sich jedoch immer wieder heraus, dass ein genereller Mangel an Daten besteht. Dieser Mangel bezieht sich nicht nur auf die Anzahl an verfügbaren Datensätzen, sondern auch auf die Anzahl an individuellen Stichproben, das heißt an unabhängigen Bildern und Videos, in bestehenden Datensätzen. Das führt wiederum zu einer schlechteren Erkennungsgenauigkeit von Ereignissen durch das neuronale Netz. Gerade im medizinischen Bereich ist es nicht einfach möglich die Datensätze zu erweitern oder neue Datensätze zu erfassen. Die Gründe hierfür sind vielfältig. Einerseits können rechtliche Belange die Datenveröffentlichung verhindern. Andererseits kann es sein, dass eine Krankheit nur sehr selten Auftritt und sich so keine Gelegenheit bietet die Daten zu erfassen. Ein zusätzliches Problem ist, dass es sich bei den Daten meist um eine sehr spezifische Domäne handelt, wodurch die Daten meist nur von Experten annotiert werden können. Die Annotation ist aber zeitaufwendig und somit teuer. Existierende Datenaugmentierungsmethoden können oft nur sinnvoll auf Bilddaten angewendet werden und erzeugen z.B. bei Videos nicht ausreichend zeitlich unabhängige Daten. Deswegen ist es notwendig, dass neue Methoden entwickelt werden, mit denen im Nachhinein auch Videodatensätze erweitert oder auch synthetische Daten generiert werden können. Im Rahmen dieser Dissertation werden zwei neu entwickelte Methoden vorgestellt und beispielhaft auf drei medizinische Beispiele aus dem Bereich der Chirurgie angewendet. Die erste Methode ist die sogenannte Workflow-Augmentierungsmethode, mit deren Hilfe semantischen Information, z.B. Ereignissen eines chirurgischen Arbeitsablaufs, in einem Video augmentiert werden können. Die Methode ermöglicht zusätzlich auch eine Balancierung zum Beispiel von chirurgischen Phasen oder chirurgischen Instrumenten, die im Videodatensatz vorkommen. Bei der Anwendung der Methode auf die zwei verschiedenen Datensätzen, von Kataraktoperationen und laparoskopischen Cholezystektomieoperationen, konnte die Leistungsfähigkeit der Methode gezeigt werden. Dabei wurde Genauigkeit der Instrumentenerkennung bei der Kataraktoperation durch ein Neuronales Netz während Kataraktoperation um 2,8% auf 93,5% im Vergleich zu etablierten Methoden gesteigert. Bei der chirurgischen Phasenerkennung im Fall bei der Cholezystektomie konnte sogar eine Steigerung der Genauigkeit um 8,7% auf 96,96% im Verglich zu einer früheren Studie erreicht werden. Beide Studien zeigen eindrucksvoll das Potential der Workflow-Augmentierungsmethode. Die zweite vorgestellte Methode basiert auf einem erzeugenden gegnerischen Netzwerk (engl. generative adversarial network (GAN)). Dieser Ansatz ist sehr vielversprechend, wenn nur sehr wenige Daten oder Datensätze vorhanden sind. Dabei werden mit Hilfe eines neuronalen Netzes neue fotorealistische Bilder generiert. Im Rahmen dieser Dissertation wird ein sogenanntes zyklisches erzeugendes gegnerisches Netzwerk (engl. cycle generative adversarial network (CycleGAN)) verwendet. CycleGANs führen meiste eine Bild zu Bild Transformation durch. Zusätzlich ist es möglich weitere Bedingungen an die Transformation zu knüpfen. Das CycleGAN wurde im dritten Beispiel dazu verwendet, ein Passbild von einem Patienten nach einem Kranio-Maxillofazialen chirurgischen Korrektur, mit Hilfe eines präoperativen Porträtfotos und der operativen 3D Planungsmaske, zu schätzen. Dabei konnten realistisch, lebendig aussehende Bilder generiert werden, ohne dass für das Training des GANs medizinische Daten verwendeten wurden. Stattdessen wurden für das Training synthetisch erzeugte Daten verwendet. Abschließend lässt sich sagen, dass die in dieser Arbeit entwickelten Methoden in der Lage sind, den Mangel an Stichproben und Datensätzen teilweise zu überwinden und dadurch eine bessere Erkennungsleistung von neuronalen Netzen erreicht werden konnte. Die entwickelten Methoden können in Zukunft dazu verwendet werden, bessere medizinische Unterstützungssysteme basierende auf künstlicher Intelligenz zu entwerfen, die den Arzt in der klinischen Routine weiter unterstützen, z.B. bei der Diagnose, der Therapie oder bei bildgesteuerten Eingriffen, was zu einer Verringerung der klinischen Arbeitsbelastung und damit zu einer Verbesserung der Patientensicherheit führt

The role of dry eye disease in cataract and refractive surgery

El síndrome de ojo seco (DED) puede jugar un papel importante en las cirugías oftálmicas con fines refractivos tanto corneales (tratamiento corneal laser) como cristalinianas (cirugía de catarata) pero también en aquellas cuyo fin es controlar la presión intraocular en pacientes que sufren de glaucoma. El objetivo principal de esta tesis se refiere a la aplicación de una serie de pruebas diagnósticas, de mínimamente a no-invasivas, sugeridas por el Tear Film & Ocular Society Dry Eye WorkShop II (TFOS DEWS II) que pueden ayudar a mejorar los resultandos refractivos y visuales en la cirugía oftálmica actual. La cirugía de cristalino, particularmente la cirugía moderna de catarata y la refractive lens exchange (RLE), centra la primera sección de la tesis. En realidad, el DED no está presente solo como complicación post-operatoria, sino que también es responsable de resultados refractivos y visuales no deseados dado que parte del examen pre-operatorio en la cirugía del cristalino puede verse influida por una película lagrimal deficiente (por ej. biometría ocular y topografía corneal). La literatura revisada ha demostrado poca información en el uso de técnicas avanzadas para evaluar la película lacrimal en pacientes que se someten a cirugía de cristalino, siendo estos hallazgos los más importantes para evitar resultados subóptimos después de la intervención. Posteriormente, en la cirugía refractiva corneal moderna, a pesar de la seguridad y efectividad en la corrección de errores refractivos tales como miopía, hipermetropía y astigmatismo, el DED post-quirúrgico sigue siendo un problema recurrente y unas de las complicaciones más referidas por los pacientes. Recientemente, nuevas técnicas (por ej. small incision lenticule extraction (SMILE)) han sido introducidas con el fin de reducir el desarrollo de DED. El uso de la microscopia confocal in-vivo, así como un programa automático de análisis, has sido incluidos para proporcionar resultados objetivos más rápido que puedan ser comparados con la cirugía de la córnea tradicional (e.g. laser-assisted in situ keratomileusis (LASIK)).El manejo de glaucoma mediante colirios oculares con preservantes puede llevar a deterioro de la superficie ocular con una larga proporción de pacientes con quejas del DED tanto como signos (como enrojecimiento ocular) tanto como síntomas (como incomodidad ocular, fotofobia, etc.). De los nuevos procedimientos oculares para controlar la presión intraocular reduciendo la necesidad del manejo tópico, la cirugía de glaucoma minimamente invasiva (MIGS) es prometedora también en mejorar la homeostasis de la superficie ocular. Sin embargo, muy poco ha sido investigado y la necesidad de una mejor comprensión ha llevado a administrar una serie de pruebas avanzadas para el diagnóstico de ojo DED con objeto de revelar los resultados a corto plazo sometidos a MIGS. Los estudios de investigación detallados en esta tesis evalúan una serie de técnicas avanzada de diagnóstico para comprender el papel de la DED en los procedimiento actuales de cirugía oftálmica con propósitos refractivos y visuales pero también para el manejo de enfermedades como el glaucoma. Asimismo, dichos estudios tratan de descubrir cual son las pruebas más importantes, mínimamente o no-invasivas, capaces de revelar el papel del DED en la cirugía oftálmica que llevarían a una mejora en los resultados tanto refractivos como visuales, así como los referidos por los pacientes.Dry eye disease (DED) can play an important role in ophthalmic procedures with refractive aims such as those involving the cornea (corneal laser surgery) or the crystalline lens (refractive lensectomy or cataract surgery) but also in the treatment of other conditions such as glaucoma. This thesis describes the application of a series of minimally to non-invasive diagnostic DED tests recommended by the recent Tear Film & Ocular Society Dry Eye WorkShop II (TFOS DEWS II) to help to improve the understanding of the impact of dry eye on the refractive and visual outcomes in the ophthalmic surgery and the impact of ophthalmic surgery on the ocular surface. Intraocular lens surgery, in particular modern cataract and refractive lens-exchange (RLE) surgery, is the focus of the first section of the thesis. In fact, DED is not only present as a post-operative complication but can also be responsible for sub-optimal refractive and visual outcomes since parts of the pre-operative examination pathway can be influenced by a depleted tear film (e.g. biometry and corneal topography). A literature review suggests little evidence of the routine use of advanced tear film assessments in patients undergoing intraocular lens surgery and there is little information on which DED findings are most important to avoid suboptimal clinical outcomes. Studies were carried out to explore the most relevant DED tests as recommended by the TFOS DEWS II. The key findings were validated questionnaires such as Ocular Surface Disease Index (OSDI) and Dry Eye Questionnaire 5-items (DEQ-5) and tear metrics such as non-invasive keratograph break-up time (NIKBUT), tear film volume (TMH) and tear osmolarity. In modern corneal refractive surgery, despite numerous publications and studies demonstrating the safety and efficacy in correcting refractive errors such as myopia, hyperopia and astigmatism, post-operative DED is still problematic and of the most common complications after surgery. Recently, newer techniques (e.g. small incision lenticule extraction (SMILE)) have been introduced with the aim of providing excellent visual outcomes whilst overcoming some of the limitations of more established procedures including undesirable alterations to corneal nerve structure and function and DED development. The use of in-vivo confocal microscopy was used to compare corneal nerve structure after SMILE with that seen after traditional laser-assisted in situ keratomileusis (LASIK). The results showed FS-LASIK surgery had more impact on DED symptomatology, TMH and NIKBUT and has led to significant change to the corneal nerve fibre metrics considered than SMILE surgery. Glaucoma management with topical preserved eyedrops can lead to deterioration of the ocular surface in a large proportion of patients with DED issues in terms of signs (e.g. ocular redness) and symptoms (grittiness, photophobia, etc.). Of the newer surgical procedures designed to control intraocular pressure reducing the need for topical management, minimally-invasive glaucoma surgery (MIGS) seems to be promising and could improve the homeostasis of the ocular surface in glaucoma patients. However, very little research on this topic has been published and an advanced pilot investigation to explore the use of a diagnostic battery of tests for DED after MIGS was carried out. Reduction in IOP was achieved by the procedure together with the reduction in DED symptomatology, increase of stability of the tear film and improvement of the ocular surface staining. In summary, the research studies detailed in this thesis use a series of advanced diagnostic techniques primarily to understand the role of DED in patients undergoing ophthalmic procedures for refractive and visual indications but also in patients being treated for glaucoma. They also explore which are the most important tests, in terms of identifying the impact of DED in ophthalmic surgery. Better diagnosis and management of DED in patients undergoing ophthalmic surgery will lead to optimal refractive, visual and patient-reported outcomes

Analysis and Correction of Corneal Astigmatism in Modern Pseudophakia

Toric intraocular lenses (IOLs) are designed to reduce spectacle dependency by correcting corneal astigmatism at the time of surgery. However, these IOLs are reliant on the accurate prediction of post-operative corneal astigmatism through reliable ocular biometry and the accurate calculation of surgically induced astigmatism. In the thesis the repeatability of assessing corneal curvature was assessed using six commercially available keratometers. The results question the validity of corneal biometry and infer that much of the apparent change in corneal shape usually associated with surgically induced astigmatism may be due to measurement error. The use of the oblique cross cylinder formulae for the calculation of post-operative corneal curvature was also investigated. This formula is incorporated into all commercially available toric IOL calculators and is utilised in every toric IOL implantation. The results from this thesis indicate that the formula is not applicable to the human cornea and that the use of the calculator does not increase the effectivity of the toric correction. Furthermore, the thesis queries the assumption that post-operative corneal astigmatism is directly proportional to post-operative refractive error. The disparity between both the magnitude and axis of astigmatism measured by keratometry and manifest refraction in a pseudophakic population was investigated. The axis measurements in particular showed very poor agreement; far outside an acceptable level of misalignment, significantly decreasing the effective correction provided if the lens was aligned with the keratometry readings. Inclusion of the posterior corneal curvature and thickness, along with a smaller chord length may lead to a more accurate assessment of corneal power. Despite the difficulty in providing an effective toric IOL correction, it was found that the correction of corneal astigmatism at the time of cataract surgery might decrease the risks of falls. Uncorrected astigmatism and cataract both cause a reduction in stability when stepping oven an obstacle, which is one of the most common causes of trips and falls in the elderly population.Plymouth Universit