This edition of 1 slide in 5 minutes covers glaucoma associated with intraocular tumors. Mechanism of IOP elevation, diagnosis and treatment methods are discussed in this short presentation.
Speaker: Dr. Malik Y. Kahook, Professor of Ophthalmology, University of Colorado, USA
Dr. Kahook: This is Malik Kahook from the University of Colorado here to discuss Glaucoma associate with intraocular tumors in this edition of one slide in 5 minutes.
Coexisting glaucoma and intraocular tumors are not a common occurrence in most ophthalmic clinics around the world. However, the coexistence of these two diseases can present unique challenges for diagnosis, treatment and follow-up.
Mechanism of IOP Elevation
• Intraocular tumors can cause elevated IOP by:
• Direct angle invasion (Metastatic seeding into the eyes, primary ciliary body or iris tumors)
• Angle closure by shifting the iris/lens diaphragm forward (retinal/choroidal tumors, ring melanomas)
• Intraocular hemorrhage with mechanical plugging of the outflow system
• Pigment plugging of the TM originating from melanomas or melanocytomas
• Formation of NVI/NVA (melanomas, retinoblastomas, post radiation ocular ischemia which can be a sequela of both proton beam radiotherapy and less frequently after plaque brachytherapy)
• Deposition of tumor/inflammatory cells on TM
• Angle closure due to posterior synechiae (inflammation) related to necrotic cells
• Steroid related glaucoma when periocular, topical and/or intravitreal anti-inflammatories are needed post radiation and inflammation
• Anti-VEGF agent related elevation in IOP
• Macrophages may engulf necrotic tumor cells and deposit in the TM with mechanical plugging
• To further complicate diagnoses, more than one cause of increased IOP might coexist. For example, neovascularization and direct tumor invasion or steroid response IOP elevation with pigment plugging of the TM.
• Pediatric tumors can also be associated with elevated IOP including: Retinoblastoma, Juvenile Xanthogranuloma, Meduloepitheliomas.
Proper diagnosis starts with detailed history (asking about systemic malignancies), slit lamp exam (with emphasis on gonioscopy and dilated fundus exam) as well as advanced imaging with ultrasound (including ultrasound biomicroscopy), optical coherence tomography and fluorescein angiography when appropriate. Consultation with other ophthalmic subspecialists is constructive with anterior segment surgeons (glaucoma, cornea) often collaborating with vitreoretinal specialists (and occasionally oculoplastics) to both identify the cancerous lesion as well as outline next steps for a holistic treatment plan. Involving primary care and oncology team members will also lead to surveillance and proper staging of the cancerous process and applies to both metastatic diseases as well as primary tumors of the eye.
The most worrisome scenario is when patients are noted to have increased intraocular pressure but without recognition of the tumor which is causing the elevated pressure. In this scenario, the eye care professional might delay proper diagnosis and treatment which could lead to loss of vision, loss of the eye or, in the worst-case scenario, metastases with life threatening consequences.
Treatment Considerations start with ensuring patient safety and not compromising the treatment of the cancer by methods used to treat the glaucoma (incisional surgery allowing for tumor metastases).
Intraocular Pressure Lowering Medications:
Prostaglandin analogues, just as is the case with most glaucomas, is the primary medication class of choice in almost all cases of tumor related IOP elevation. Caution must be taken in cases where tumors are being followed in the anterior segment of the eye and prostaglandin analogues induce changes in pigmentation which could be confused as tumor extension. This concern is however typically related to iris melanomas and not other intraocular tumors. When there is concern in these rare cases, other classes of topical therapeutics can be used. Worries about enhancing conventional and non-conventional aqueous humor outflow leading to liberation of tumor cells out of the eye have not been validated in any study. In fact, there is no clear contraindication to the use of any class of topical IOP lowering medications and the treating physician should use their typical algorithm with the primary goal of decreasing pressure and preserving optic nerve function.
All filtration surgeries should be avoided in cases where active tumor exists in the eye. There are documented cases of intraocular tumor cells being liberated from inside of the eye to filtration blebs when tumors are not recognized prior to glaucoma surgery. In cases where radiation has already been completed and tumor egress is noted, filtration surgery, including glaucoma drainage device (GDD) implantation, is a valid choice and has been proven successful in published literature. There is a dearth of data on use of angle procedures such as goniotomy or TM bypass devices in this setting. However, it would be reasonable, in cases where tumors have been treated successfully, to consider angle-based procedures as safe by using filtration surgeries such as GDDs as a reference point.
There are several laser-based options for the reduction of IOP. These include both non-invasive options, like Selective Laser Trabeculoplasty (SLT) and Trans-Scleral Cyclophotocoagulation (TS-CPC), and invasive options like endocyclophotocoagulation (ECP). TS-CPC is in fact our primary method for treating IOP with coexistent intraocular tumors because of the non-invasive nature, ability to retreat and lack of plausible tumor cell liberation compared to filtration surgery and other treatment modalities. It is important to note that tumor spread has not been noted with any of these laser options and any concerns, for example spread of tumor past TM and into the canal of Schlemm post SLT, are purely theoretical. Our service considers SLT as a viable option when more modest IOP lowering is needed or when temporizing measures are needed during the time the primary tumor is under treatment.
Lowering IOP in eyes with co-existent glaucoma and intraocular tumors can be challenging and multiple considerations must be taken into account for both of these complex diseases. Fortunately, with proper diagnosis, IOP is frequently controlled with the measures noted above and the primary tumor can undergo treatment to preserve vision and avoid systemic complications. Outcomes are worse when tumors are only recognized post invasive filtration surgery which may allow for tumor cells to be released from the eye with possible distant seeding. This highlights the need to be cognizant of the possibility of co-existent glaucoma and intraocular tumors and to look for clues on physical exam including gonioscopy (deep pigmentation and/or masses in the angle), iris pigmentation (sectoral and/or changing over time), iris masses and fundus examination to rule out posterior pole tumors.
Shukla AG, Vaidya S, Yaghy A, Razeghinejad R, Mantravadi AV, Myers JS, Kaliki S, Shields CL. Transscleral Cyclophotocoagulation for Glaucoma in the Setting of Uveal Melanoma. Ophthalmol Glaucoma. 2020 Sep 18:S2589-4196(20)30256-8.
Camp DA, Yadav P, Dalvin LA, Shields CL. Glaucoma secondary to intraocular tumors: mechanisms and management. Curr Opin Ophthalmol. 2019 Mar;30(2):71-81.