Eye surgery – basic research, epidemiology and clinical trials

Pathogenesis in cataract and age-related macular degeneration

Oxidative stress and protein aggregation

Lens opacities are caused by disturbances in the lens’ normal fibre structure and/or by damage to lens proteins from oxidative stress, resulting in light scattering protein aggregates. The ability to prevent such aggregates, especially through the ubiquitin proteasome system (UPS), is a corner stone in cellular defence against ageing. The cataract group studies protein modifications in cataractous lenses and regulation of the UPS in cultured lens epithelial cells and in animal models to increase knowledge of cataractogenesis. Cell and molecular biology techniques are employed as well as targeted proteomics. Oxidativ stress and protein aggregation are also important features in the pathogenesis of age-related macular degeneration, AMD. The research group has recently developed a cell model to examine these mechanisms in retinal pigment epithelial cells (RPE). Dinna Zhou, MD, is PhD student in this project with Madeleine Zetterberg (MZ) as main and Anne Petersen and Malin Hernebring as co-supervisors. Parts of these projects are conducted in collaboration with researchers at Astra Zeneca; among those Julia Adelöf, postdoc and previous PhD student in the research group.

Cataract epidemiology – current cohorts and ongoing register-based studies

Prevalence of lens opacities and previous cataract surgery in 70-year-olds – risk factors and importance for visual function and vision-related quality of life

The yearly number of cataract extractions in Sweden and at each Swedish eye clinic can be obtained through the Swedish National Cataract Register; NCR. However, there is no data on the proportion of people already subjected to cataract surgery in the population, as well as the prevalence of lens opacities requiring surgery, information that is valuable in order to predict the future need for surgery. The research subjects in this project were recruited from the H70-study, a large epidemiologic study on 70-year old people in Gothenburg, conducted by professor Ingmar Skoog at the Memory Clinic at Sahlgrenska/Mölndal. Visual acuity, visual field and lens photography with classification and grading of lens opacities have been performed. Lena Havstam-Johansson and Moa Nordström are PhD students in this project. The former is also investigating vision-related quality of life and visual function in general in Swedish 70-year-olds.

Are there occupational exposures that increase the risk of cataract?

Historically, there is a known association between cataract and working as a glass-blower, which is considered being due to infrared radiation. More recent studies on occupational exposure and cataract is missing, however. In collaboration with docent Mathias Holm and professor Kjell Torén at the Department of Occupational and Environmental Medicine at Sahlgrenska University Hospital, an epidemiologic study on occupational exposure and cataract has been initiated. In 2014, questionnaires were sent to all 63-year-old persons in Region Västra Götaland regarding eye diseases, previous cataract surgery, occupational and environmental exposure. Possible associations with occupational (welding, passive smoking etc) and environmental (UVB from outdoor work) exposure are being analysed.

Cataract surgery in patients with ocular co-morbidity

Based on data from the cataract register, differences in visual acuity before and after cataract surgery, as well as the risk for intraoperative difficulties and complications, were compared between patients with and without diabetic retinopathy (DRP). Patients with DRP had almost twice as high risk of intraoperative complications compared to patients without DRP. They also had worse visual acuity both before and after surgery compared to patients without DRP but the improvement in visual acuity after surgery was similar.

Relation between operation volume, case mix index and rate of complications

In studies from the cataract register we were able to demonstrate that the proportion of high volume cataract surgeons (>500 procedures yearly) has increased substantially between 2007 and 2016. High volume-surgeons had significantly lower frequency of posterior capsule rupture but also a lower proportion of patients with risk factors for complicated surgery, i.e. lower case mix index. Based on data from 2016 we could demonstrate that a surgeon needs a volume of at least 400 procedures/year in order to have a complication rate of 1% or less, something that is considered golden standard in cataract surgery benchmarking.

Surgical management

Paediatric cataract – optimal surgical management

Even though the majority of cataract patients are elderly, congenital cataract is a major clinical problem. This is despite its rareness; in Sweden 1 per 40,000 births. Without surgery, congenital cataract leads to substantial visual impairment or even blindness. Early discovery and surgery, before three months of age, is necessary since visual pathways and higher visual functions are dependent on early visual stimuli. The earlier surgery is performed, the bigger is the chance of the child having a normal visual development. The risk for complications however, such as secondary glaucoma, is higher with early surgery. Together with colleagues at the Ophthalmic department at Sahlgrenska/Mölndal, the cataract research group conducts studies on surgical management in this patient group, aiming to pinpoint the optimal age for surgery, the best choice of intraocular lens and how to minimize complications. This research resulted in a dissertation in 2019 when Alf Nyström, senior consultant and head of intraocular pediatric surgery, presented his thesis.

What intraocular lens should be used in patients with ocular comorbidity?

In patients with ocular comorbidity, such as persons with intraocular inflammation, uveitis, the risks of complications at cataract surgery may be increased. Uveitis patients have a higher risk of severe postoperative inflammation and posterior capsule opacification, after-cataract. It has been suggested that the type of intraocular lens prosthesis implanted in the eye at surgery may influence the risk of these complications. Within the cataract group, studies are conducted where the importance of the lens material for the degree of postoperative inflammation and after-cataract is investigated. Sara Pålsson is a PhD student in this project.

Another group of patients where the choice of intraocular lens prosthesis is difficult is in persons with degenerative corneal diseases such as keratoconus. The technical advancement of lens prosthesis is rapid and lenses compensating for astigmatism (different refractive power in different angles of the cornea) exist but whether these can be used in keratoconus has not been ascertained. The cataract group is conducting research to elucidate the optimal intraocular lens for these patients.

Complications to cataract surgery

For the majority of all patients, cataract surgery is a routine procedure with a low complication rate. Complications, some of which potentially vision threatening, occur however and since cataract extraction is so common (about 110,000 procedures in Sweden in 2015), the number of affected patients is still large. Some of the complications affect the posterior segment of the eye; the vitreous and retina. It is known that previous eye surgery increases the risk of retinal detachment, often within the first postoperative months. The cataract group conducts studies to determine the size of this increase, what risk factors contribute and how to minimize the influence of these.

Another complication that may occur, often several years after cataract surgery, is dislocation of the intraocular lens prosthesis, leading to visual impairment. Several techniques exist to reposition the existing lens prosthesis or to exchange it to a new one. The cataract group performs studies aiming to elucidate the optimal surgical strategy in these patients.

Group members

Madeleine Zetterberg, Principal Investigator

Julia Adelöf
Marcelo Ayala
Lena Havstam Johansson
Malin Hernebring
Gunnar Jakobsson
Lada Kalaboukhova
Pia Kvickström
Moa Nordström
Alf Nyström
Anne Petersen
Sara Pålsson
Thiemo Rudolph
Joanna von Hofsten
Wolf Wonneberger
Dinna Zhou