Ophthalmic research

The research within our LUMC departments is conducted within departmental research programmes. The research programme below is embedded within the department of Ophthalmology.

Aim and focus

The Department of Ophthalmology focusses on four clinically-relevant areas: ocular oncology, retinal diseases, paediatric ophthalmology and cornea and refractive surgery.  Clinical and translational research is disease initiated, and involves improving diagnoses, prognosis, treatment and individualized eye care. The department has a strong collaboration with the laboratories of Clinical Oncology and Molecular Cell Biology for the translation of clinical questions into laboratory research, including animal studies, in order to help patients.

The LUMC is the national referral center for the diagnosis and treatment of ocular melanoma as well as of other tumors of the eye and orbit. The NFU has allocated the LUMC the status of Center of Expertise for Uveal Melanoma. The LUMC is the only center in the Netherlands which offers local brachytherapy. Clinical research involves improving local irradiation, and the prevention and treatment of radiation-related complications. Innovative high resolution ocular MRI techniques lead to non-invasive image-guided methods to further personalise the diagnosis and treatment planning of uveal melanoma. Translational research focusses the development of new targeted (molecular pathway and immunological) therapies. Analysis of uveal melanoma tissues shows that loss of expression of BAP1, a de-ubiquitinase, leads to metastases and is associated with the presence of an inflammatory phenotype. Germline mutations in BAP1 lead to a tumor predisposition syndrome, which includes eye and skin melanoma. Identification of families with this syndrome is a priority.

Retinal diseases
Retinal diseases such as hereditary dystrophies, age-related macular degeneration, and central serous chorioretinopathy are among the main causes of vision loss and blindness in the Western world. The LUMC is a regional and national referral center for retinal diseases. Research focusses on the safety and efficacy of new treatments (investigator-initiated and industry-driven trials), basic research on pathogenesis including induced pluripotent stem cell (iPSC) studies, tailored treatment through gene therapy and stem cell therapy for patients with hereditary retinal dystrophies, and prospective natural history studies to prepare for this gene therapy.

Paediatric ophthalmology
Paediatric ophthalmology combines almost all medical subspecialties in ophthalmology into one, as patients often suffer from complex conditions. The LUMC is a national referral center for the diagnosis and treatment of vision-threatening eye diseases such as uveitis, cataract, lens subluxation, albinism and retinal diseases in children, and has been recognized by the NFU as a Center of Expertise for the treatment of Retinopathy of Prematurity (ROP). The main research focus is on retinal diseases, especially those diseases with abnormal angiogenesis such as ROP and Coats disease. An LUMC-initiated national inventory on treatment results of ROP from 2010-2016 will result in better insight in treatment modalities and logistics (NEDROP 1 (2009) and 2 (2017)). As blood vessels and oxygenation are the topic of interest in ROP and Coats, a handheld oximeter to image ocular oxygenation and blood vessel diameters has been developed and several research projects have been launched (ROPOXYMAP, ROPCORIMAP).

Cornea and refractive surgery
Modulation of the cornea by laser or implantation of anterior-chamber lenses can be applied to change refractive aberrations. Increasingly, corneal transplants are no longer full thickness but involve specific layers. Long-term follow-up is important to see the outcome of these treatments. An artificial cornea is being developed as a last resort device. The role of peripheral vision is studied combining, biomedical imaging, optical simulations and psychophysical tests, to improve peripheral vision after cataract surgery and understand specific complications after cataract surgery such as dysphotopsia.

Position in international context

  • The Dept of Ophthalmology is one of the few centres worldwide where top clinical care in ocular oncology is combined with extensive translational and basic research. Collaborations exist with the European Ophthalmic Oncology Group, International Society of Ocular Oncology, International Ocular Inflammation Society, Schepens Eye Research Institute, Boston, The Cancer Genome Atlas Project, the American Joint Committee on Cancer; the LUMC participates in a Horizon CURE UM grant, and in Eurocan (European Network of Cancer Centers of Excellence).
  • The new focus on regenerative therapies in retinal diseases starts to bear fruit and participates in the European Reference Network for Rare Eye Diseases (ERN-EYE), UCAN CAN-DU, and the European Training Network.
  • The focus on ROP has led to strong collaborations within EPOS (European Pediatric Ophthalmology Society) and the group of Prof E. Stefansson, University of Reykjavik, Iceland (oximetry)
  • Participation in the Dutch Society for Refractive Surgery, ESCRS, ASCRS, COST on corneal regeneration, and in the Horizon2020 grant Arrest Blindness

Content / highlights / achievements

  • Loss of BAP1 expression determines malignancy of uveal melanoma and an inflammatory phenotype
  • Uveal melanoma can be separated into four genetically and immunologically specific subtypes
  • Development of new animal models for metastatic uveal and conjunctival melanoma (mice, zebrafish)
  • Nevi already carry a GNAQ/GNA11 mutation
  • First prospective multicenter randomized controlled treatment trials for central serous chorioretinopathy (PLACE trial, SPECTRA trial)
  • National screening for retinopathy of prematurity is effective
  • Development and validation of a handheld oximeter
  • Development of Patient-specific 3D eye-models for refractive surgery and proton beam therapy
  • Proof of concept for gene therapy in animals with early-onset retinitis pigmentosa due to mutations in CRB1

Future themes

  • Reduce side effects of radiation treatment of ocuar tumors 
  • Develop targeted and immune therapy for eye melanoma metastases 
  • Image-guided proton beam treatment for uveal melanoma
  • Early identification of high-risk individuals who carry a mutation in the BAP1 gene
  • Use of iPSC cells to determine the function of BAP1 in the epigenetic regulation of inflammation and uveal melanoma cell growth
Retina/ Pediatric ophthalmology
  • Investigator-initiated prospective randomized controlled trials for central serous chorioretinopathy 
  • Genetic studies in central serous chorioretinopathy and age-related macular degeneration
  • Prospective natural history studies in preparation for gene therapy studies for hereditary retinal diseases
  • iPSC studies for the development of new gene and stem cell therapy
  • Clinical gene therapy for patients with early-onset retinitis pigmentosa due to mutations in CRB1
  • NEDROP-2 to evaluate results of NEDROP
  • Improve early diagnosis and treatment in prematurely-born infants with ROP by oxymetry.
  • Evaluate treatment effectiveness in ROP.
Cornea and refractive surgery
  • Develop a clinically-applicable artificial cornea
  • Long-term follow up of implanted anterior chamber lenses
  • 3D eye modelling for intraocular lens technology