Older patient presents with hypermature cataract, angle-closure glaucoma
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A 73-year-old white woman was referred to the retina service at the New England Eye Center for consideration of pars plana vitrectomy and lensectomy in the right eye for a hypermature cataract and angle-closure glaucoma.
At the time of presentation to the New England Eye Center, she complained of blurry vision in the right eye but denied pain. She was taking oral acetazolamide 500 mg twice per day, combination brimonidine-timolol twice per day and bimatoprost at night in the right eye.
Her ocular history included anatomic narrow angles in both eyes, and she was status post laser peripheral iridotomy in the right eye 1 week before presentation. She had strabismic amblyopia in the right eye. She had been followed in the past for dry eyes, posterior vitreous detachment in the left eye and nuclear sclerotic cataracts in both eyes. Before this acute episode, she had not seen an ophthalmologist in 4 years.
Her medical history included hypertension and hyperlipidemia. Aside from the recent laser peripheral iridotomy, she had never had ocular surgery. Her medications included hydrochlorothiazide, lisinopril, aspirin 81 mg and atorvastatin. Her family history included breast cancer, ovarian cancer, hypertension and diabetes.
She was a former certified nursing assistant. She was a former smoker with a cumulative 40 pack-year smoking history. She occasionally consumed alcohol. She had recently quit driving due to her decreased vision.
Examination
On exam, the patient’s visual acuity was count fingers at 1 foot in the right eye and 20/25 in the left eye. Vision did not improve with pinhole testing. Confrontation visual fields showed constriction in the right eye and were full in the left eye. IOP in the right and left eyes was maintained at 12 mm Hg on oral acetazolamide 500 mg twice daily, brimonidine-timolol twice daily and bimatoprost at night in the right eye. Extraocular movements were full, and alignment showed right esotropia consistent with her known history of strabismus. Both pupils were reactive to light without a relative afferent pupillary defect.
External exam, lids and lashes were normal in both eyes. On the right, the conjunctiva showed 1+ injection with a prominent temporal vessel, the cornea appeared clear, and the anterior chamber was uniformly shallow. She had a patent superior peripheral iridotomy. She had a brunescent cataract with pigment on the anterior lens capsule. Exam of the left eye was unremarkable except for narrow angles with 2+ cortical and nuclear sclerotic cataract. She was unable to tolerate gonioscopy at this visit, but her previous provider had noted that there were no angle structures visible in both eyes.
There was no view to the fundus in the right eye, and the exam of the posterior segment was normal in the left eye with a small cup-to-disc ratio and no evidence of glaucomatous change to the nerve.
What is your diagnosis?
See answer below.
Narrow angles, cataract
This patient has elevated IOP in the setting of narrow angles and advanced cataract, suggestive of secondary phacomorphic angle-closure glaucoma in a shallow, predisposed eye. Without a clear view to the fundus in the right eye, however, it is essential to consider other forms of secondary angle-closure glaucoma.
Causes of secondary angle-closure glaucoma can be categorized into those etiologies that cause pupillary block and those that do not cause pupillary block.
Pupillary block, or the interruption of aqueous flow from the posterior chamber to the anterior chamber, can be caused by pupillary apposition of the lens with a dense cataract, ectopia lentis or the vitreous face in an aphakic eye. Patients with an anterior chamber IOL are also at risk for pupillary block if the surgeon does not create an iridotomy or if the lens haptic blocks flow through the iridotomy.
Secondary angle closure without evidence of pupillary block may be caused by a “push” mechanism, with posterior pressure resulting in closed angles, or by a “pull” mechanism, with anterior displacement of the iris by a contractile process. “Push” pathologies include aqueous misdirection, exudative retinal detachment with or without choroidal effusion, drug-induced anterior rotation of the ciliary body or persistent fetal vasculature, or it could occur in the setting of prior retinal surgery. Nanophthalmic eyes are prone to spontaneous choroidal effusion as well. “Pull” mechanisms include neovascular glaucoma with peripheral anterior synechiae (PAS), iridocorneal endothelial syndrome, or epithelial ingrowth or downgrowth.
Intraocular tumors and inflammatory etiologies can cause a combination of “push” or “pull” closure of the angle. A tumor can directly push by mass effect or cause posterior pressure via exudative detachment and choroidal effusion. It may also cause inflammation or ischemia, with resulting PAS that blocks the angle.
Our patient’s history and exam were not consistent with several of these etiologies; she had no history of ocular surgery, and she had no findings on exam that would suggest iridocorneal endothelial syndrome or epithelial downgrowth.
Posterior pathologies such as choroidal effusion, exudative detachment, ischemic process causing neovascular glaucoma, or tumor remained on the differential.
Workup and management
With no view to the posterior pole in the right eye, B-scan was performed to evaluate other causes of secondary angle-closure glaucoma (Figures 1 and 2).
Source: Erin Lanzo, MD, Shilpa Desai, MD, Alison Callahan, MD, and Nora Laver, MD
At this time, there was confirmation of posterior pressure secondary to a large intraocular mass. Given the characteristics noted on B-scan, notably the dome shape, low-internal reflectivity and intact retina, the mass was localized to the choroid and was thought to be a primary choroidal melanoma.
The patient underwent laboratory testing (complete blood count and liver function tests), chest X-ray and MRI of the abdomen to evaluate for metastasis of a presumed choroidal melanoma.
Given the size of the tumor measured on B-scan, enucleation was an early consideration but was not yet definitive. For this reason, diagnostic and therapeutic cataract surgery was planned to address the angle-closure glaucoma and to better visualize the mass. Preparations for cataract surgery were made, and A-scan measurements confirmed short axial lengths (21.62 mm right eye, 21.71 mm left eye) and shallow anterior chamber depths (1.27 mm right eye, 2.78 mm left eye).
Discussion
Uveal melanoma is the second most common intraocular tumor after choroidal metastasis. Primary choroidal melanomas are rare and occur at an incidence of approximately 5.1 per 1 million. Risk factors include light iris and skin color, tendency to freckle, northern European ancestry, welding, family history of uveal melanoma, presence of choroidal nevi and presence of nevus of Ota (with an incidence of melanoma of one in 400 in these patients).
Posterior uveal melanoma is more common than anterior uveal melanoma. Anterior uveal melanomas, which include choroidal melanoma anterior to the equator, ciliary body melanoma and iris melanoma, account for 9% to 15% of uveal melanomas.
Patients present with symptoms including blurry vision (38%), photopsias (9%), floaters (7%), visual field loss (6%), visible tumor (3%), pain (2%) and metamorphopsia (2%). Notably, 30% of patients are asymptomatic.
The following characteristics should prompt further investigation of a suspicious lesion: a gray-brown appearance (although amelanotic tumors may appear yellow), greater than 2 mm thickness, presence of subretinal fluid, presence of orange pigment, presence of sentinel vessel and presence of secondary glaucoma. Drusen and a halo of depigmentation around a pigmented choroidal lesion may suggest a benign nevus.
B-scan and enhanced depth imaging spectral-domain OCT are useful imaging modalities to characterize a choroidal lesion. If melanoma is suspected, blood work including liver function tests and imaging of the chest and abdomen should be pursued promptly to evaluate for distant metastasis.
Secondary glaucoma from intraocular tumor occurs in 3% to 20% of patients via varied mechanisms, either in isolation or in combination. There may be anterior displacement of the lens-iris diaphragm from posterior pressure, tumor cell-indicated PAS, ischemic necrosis of the tumor or exudative retinal detachment causing neovascular glaucoma, or tumor-associated inflammation leading to posterior synechiae, pupillary block and/or PAS. There may also be direct angle invasion by a ring melanoma of the ciliary body, seeding of the angle by malignant cells or phagocytosed melanin pigments causing melanomalytic glaucoma.
In a 1987 survey of 2,704 eyes at Wills Eye Hospital, Shields and colleagues found that 126 of the tumor-containing eyes had tumor-induced elevated IOP at the time of diagnosis. Of those with uveal melanoma, secondary IOP elevation was present in 55 eyes (3%). Within that study population, angle-closure glaucoma was present in cases of choroidal metastasis but not in primary choroidal melanoma. Since that time, there are reports of angle-closure glaucoma as the presenting sign in cases of uveal melanoma. Many of these eyes had poor outcomes due to delay in diagnosis; on occasion, an eye underwent glaucoma filtering surgery to treat angle closure before a tumor diagnosis was made.
Laser peripheral iridotomy to treat angle-closure glaucoma in an eye with an intraocular tumor is controversial and may lead to dissemination of the tumor, particularly with the photodisruptive YAG laser. One study has described palliative cyclophotocoagulation for the treatment of secondary glaucoma in eyes with uveal melanoma, which resulted in relief of pain in all patients but often with poor visual outcomes.
Prompt referral to radiation oncology is indicated for consideration of plaque brachytherapy, proton beam radiotherapy or gamma knife radiotherapy. Plaque brachytherapy is useful for tumors less than 18 mm in diameter and can usually penetrate 10 mm in thickness. Proton beam radiotherapy may treat larger choroidal melanomas and melanomas close to the optic disc. Gamma knife therapy may be an option in a similar manner as proton therapy and may be more readily available to patients. Less commonly, transpupillary thermotherapy, photocoagulation and photodynamic therapy have been pursued in treatment of choroidal melanoma. Enucleation is an option if the patient is not a good candidate for radiotherapy based on tumor characteristics and has a secondary benefit of enabling a pathologic diagnosis. If pathologic diagnosis is required but enucleation is not planned, biopsy through the sclera would be an alternative option.
Case resolution
Our patient underwent cataract surgery with phacoemulsification via clear corneal incision to better visualize the tumor. Trypan blue, epi-Shugarcaine and Healon GV (1.8% sodium hyaluronate, Johnson & Johnson Vision) were used to better visualize the anterior capsule, to aid in pupillary dilation and to maintain depth in a shallow anterior chamber. A 25-gauge needle was used to drain the lens before capsulorrhexis; despite this cautionary step, an “Argentinian flag” sign still occurred. The surgeon was able to use a Seibel chopper to extract the lens without disruption of the posterior capsule. An intraoperative posterior exam was notable for a large pigmented choroidal mass extending past the visual axis and anteriorly to the lens capsule. The peripheral retina was flat. No IOL was implanted.
The patient had a clear chest X-ray and no evidence of metastatic disease on abdominal imaging and laboratory workup. She was referred to radiation oncology. She was not a candidate for plaque brachytherapy given the size of the tumor. Gamma knife therapy was offered with the caveat that the likelihood of local control was decreased compared with cases of smaller tumors.
Ultimately, the patient opted for enucleation. Pathologic diagnosis and genetic analysis were performed, giving further insight into tumor behavior and her need for future surveillance.
On pathologic analysis, a large mixed cell type melanoma was described (Figure 3). The anterior chamber also showed closed-angle glaucoma with tumor present along the anterior edge of the iris. The pathologic stage was stage IIIA.
Castle testing, which provides a gene expression profiling assay, can be useful as a prognostic indicator of tumor behavior and likelihood of metastasis. It categorizes patients in class 1A, 1B and 2, with 98%, 93% and 50% change of metastasis-free survival at 3 years and 98%, 79% and 28% metastasis-free survival at 5 years, respectively. The patient presented in this case was class 1B.
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- For more information:
- Erin Lanzo, MD, Shilpa Desai, MD, Alison Callahan, MD, and Nora Laver, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.
- Edited by Allison V. Coombs, DO, MS, and Nisha S. Dhawlikar, MD, MPH. They can be reached at New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.