GLAUCOMA IN INTRAOCULAR TUMOUR

By- Shweta .S. Maurya 3nd year B. Optometry Institute For Technology And Management

GLAUCOMA Glaucoma is the

second leading cause of blindness.

Glaucoma is actually a group of diseases. The most common type is hereditary.

INTRAOCULAR TUMORS Intraocular tumors are rare causes of

glaucoma. The epidemiology, prognosis, and

mechanism of action depend on the specific tumor type.

The tumor may not be directly visible in some instances, and different methods of indirect visualization may need to be used.

PATHOPHYSIOLOGY There are a number of different

mechanisms by which ocular tumors can cause glaucoma:

(1) Pigment dispersion, (2) Secondary angle closure(3) Uveitis,(4) Iris neovascularization,

(5) Choroidal detachment, (6) Suprachoroidal hemorrhage, and (7) Anterior displacement of lens-iris diaphragm.

THE MOST COMMON INTRAOCULAR TUMOR CAUSING SECONDARY GLAUCOMAMelanoma arising within the iris.Melanoma arising within the ciliary body.Direct growth of the tumor into the angle.Tumor seeding into the angle.

Neovascularization of the angle,Hemorrhage with volume effect or angle closure,Pigment release into the aqueous, the

surface of the iris, and the chamber angle.

PATHOPHYSIOLOGY

I. OPEN ANGLE GLAUCOMA1. Direct Invasion of Anterior Chamber Angle. mechanically

Invasion of the tumor cells in AC angle

Blocks aqueous humor from leaving the eye

Rise in IOP

2. Secondary Pigmentary Glaucoma.Massive dispersion of pigment

displaced from tumor cells (i.e.- melanoma and melanocytoma) can lead to obstruction of the AC angle.

In ciliary body melanomas this is the most common cause of secondary glaucoma.

3. Melanomalytic Glaucoma.Melanomalytic glaucoma is secondary to

the release of pigment from tumor cells which subsequently get taken up by macrophages.

Based on studies , these pigment-laden macrophages cause blockage of the trabecular meshwork which leads to increased IOP

Trabecular meshwork seeding (melanomalytic). Slit-lamp photography shows collections of episcleral perilimbal pigment deposition (arrows).

NEXT Episcleral venous hypertension due to

traumatic carotid-cavernous fistula ”

4. Increased Episcleral Venous Pressure. Aqueous humor outflow is dependent on the

pressure gradient between IOP and episcleral venous pressure.

Orbital tumors or extraocular extension of an intraocular tumor can cause an increase in episcleral venous pressure through direct compression.

Due to this pressure gradient reduction from the elevated episcleral pressure, there is a rise in IOP often causing a secondary glaucoma.

II. CLOSED ANGLE GLAUCOMA

1. Uveitic. Inflammation secondary to intraocular tumors can cause peripheral anterior

synechiae, which can lead to closure of the angle and elevation in IOP.

In patients with uveal melanomas and uveitis, secondary angle closure is common from peripheral anterior synechiae.

Metastatic tumors also have been shown to have significant inflammation leading to peripheral anterior synechiae.

2. Secondary Neovascularization. Patients with intraocular tumors can often

develop neovascularization of the iris and angle, which can lead to angle closure glaucoma.

This is commonly true in tumors which cause a chronic RD ,leading to ischemia of the tissue and resultant secondary neovascularization.

Metastatic cutaneous melanomas also are highly associated with neovascularization. Neovascularization can also present as a complication of tumor treatment.

3. Anterior Displacement of Lens-Iris Diaphragm. The most common mechanism of angle

closure in patients with intraocular tumor is forward displacement of the lens-iris diaphragm.

The displacement is usually from a large mass in the posterior segment of the eye causing forward pressure of iris and lens structures leading to pupillary block, C iris bombé and finally peripheral anterior synechiae closing the AC angle.

DIAGNOSIS

HISTORY The workup begins with a thorough history,

which should be performed in all patients with elevated IOP.

A thorough history includes all of the following:• Complete history of present illness (including current and past symptoms)• Past medical and ocular histories • Past surgical history (including radiation treatments)• Medication list (including eye drops)• Family history (especially cancer history)• Complete review of systems• Social history (including drugs, tobacco use, alcohol and occupation)

SYMPTOMS The symptoms that the patient experience

depend greatly on the type and location of the malignancy as well as the amount of ocular involvement.

The most frequently recorded symptoms are blurred vision, pain, redness and floaters.

Some patients, however, will not complain of any symptoms.

Glaucoma symptoms are dependent on the speed at which the pressure rises.

With acute glaucoma from angle closure, decreased vision, halos around lights, ocular pain, and nausea may be present.

With chronic glaucoma with progressive angle closure or open angles, no ocular symptoms related to the elevation of IOP may be present.

With iris melanoma, a hyperchromic heterochromia may be present.

With a ciliary body melanoma, a distorted pupil or vision change from lenticular astigmatism may occur.

With choroid melanoma, the visual symptoms may be decreased vision or a change in the peripheral vision, depending on the location of the tumor.

PHYSICAL EXAMINATION Slit lamp biomicroscopy Gonioscopy of the angle. A complete dilated exam, as long as the

AC angle is not too narrow. The following findings are essential to note

for any patient suspected of having tumor induced secondary glaucoma.

ANTERIOR SEGMENT EXAM FINDINGS: Pigment dispersion in AC or angle, Dilated episcleral vessels, Hyphema, Neovascularization of Iris or Angle,

o Intraocular inflammation noting cell/flare, hypopyon,o Mass lesions of the iris/ciliary body/angle,o Transillumination of globe (tumors create shadows)o Open versus closed angle

POSTERIOR SEGMENT FINDINGS:

Retinal detachments, Posterior segment masses, Vitritis, Vitreous hemorrhage.

PHYSICAL (DIAGNOSIS) Diagnosis is assisted by Gonioscopy, indirect

ophthalmoscopy, and ultrasonography. Clinical scenarios depend on tumor location.Iris melanoma can occur as either diffuse or

well-circumscribed forms, with the former being less common and more malignant.

Ciliary body melanomas tend to be larger at presentation due to their obscure location and usual lack of visual symptoms.

They may present as a ring melanoma, which completely encircles the ciliary body. Proportion of epithelioid cells is higher in ciliary body melanoma.

Choroidal tumors associated with glaucoma typically have broken through the Bruch membrane and are mushroom shaped.

Diagnosis of melanocytoma is through direct visualization using slit lamp, Gonioscopy, or indirect ophthalmoscopy.Melanocytomas can occur anywhere along

the uveal tract, although the optic nerve is the most common site.

These appear as darkly pigmented, isolated lesions, which have a strong tendency to undergo necrosis and fragmentation, leading to pigment release.

• Consequently, trabecular meshwork becomes obstructed, leading to IOP elevation.• Treatment of melanocytoma consists of observation with photographic documentation in smaller lesions.

Benign iris melanocytic lesions (Iris nevi) are difficult to grossly distinguish from malignant lesions of the iris.These occur as small, discrete, flat, or

slightly raised nodules with variable pigmentation.

Another study identified 5 factors associated with higher risk of malignancy, as follows:

(1) Diameter greater than 3 mm, (2)Pigment dispersion, (3) Prominent tumor vascularity, (4) Increased intraocular pressure, and (5) Tumor-related ocular symptoms.

Although iris nevi rarely cause a pathologic process, diffuse growth can cause elevated IOP by direct extension into the trabecular meshwork.

The treatment of an iris nevus consists of observation with photographic documentation in smaller lesions.

Tumors of the retina (retinoblastoma)The tumor may assume an endophytic or

exophytic configuration. In the former configuration, tumor cells may invade into the vitreous and anterior chambers.

Neovascularization is associated with angiogenic factor production from the tumor or ischemia due to large retinal vasculature involvement.

Subsequent neovascularization of the iris with angle closure accounts for 73% of glaucoma.

Pupillary block leading to angle closure from large tumors and infiltration of the trabecular meshwork account for the remaining cases.

RETINOBLASTOMA

OPHTHALMIC IMAGING

1. B-Scan Ultrasonography (B-Scan) If there is opacification of the media

obstructing the examiner’s view. It is helpful in taking measurements of the

posterior segment tumors like uveal melanomas and looking for concurrent RD , vitreous hemorrhage or vitritis.

2. Ultrasound Biomicroscopy (UBM) To further characterize tumors in the anterior

segment, ultrasound biomicroscopy can be performed.

UBM uses a high frequency wavelength which allows for accurate measurements of anterior lesions which is helpful for diagnosis (solid versus cystic masses).

CAUSESIntraocular tumors that may cause

elevated IOP may be of 3 types1. Melanocytoma(benign)2. Malignant melanoma3. Metastatic (spreading )

IT CAN ARISE FROM IRIS

CILIARY BODY

CHOROID

OPTIC NERVE

RETINACarcinomaCutaneous melanoma

METASTATIC TUMORS The 2 most common sites of primary tumor

metastatic to the eye are breast and lung cancers

The posterior uvea is the most common site of metastases, but glaucoma more often is associated with anterior metastases.

Mechanism of glaucoma includes direct invasion of the trabecular meshwork by tumor cells, secondary angle closure by anterior displacement of the lens-iris diaphragm, and neovascularization of AC angle.

Squamous cell carcinoma may produce a sheet of tumor cells.

Glaucoma may be the initial presentation in some patients.

Medical management of IOP coupled with radiation or chemotherapy may be useful.

Enucleation is reserved for blind, painful eyes.

PHAKOMATOSES Phakomatoses are a group of

hamartomatous disorders in which abnormal proliferation of tissues occurs in their normal locations.

These tumors primarily affect the eye, skin, and nervous system, although other systems may be affected to a lesser degree.

Neurofibromatosis is a common autosomal dominant systemic disorder divided into types 1 and 2Glaucoma usually is unilateral and associated

with eyelid thickening and contour abnormalities.

Different mechanisms for elevated IOP have been proposed, as follows:

(1) Direct infiltration of the angle tissue, (2)Secondary angle closure due to ciliary body

and choroid thickening, (3)Fibrovascular membrane formation over the angle.

MISCELLANEOUS TUMORS

MISCELLANEOUS TUMORS The eye may become involved in acute and

chronic lymphocytic leukemia and affect the anterior and posterior segment.Elevated IOP results from outflow obstruction

secondary to iritis, hyphema, hypopyon, or leukemic infiltration of the trabecular meshwork and Schlemm canal, as well as episcleral tissue, which may involve aqueous veins.

Management is primarily through medical means to control IOP and to address the underlying leukemia through appropriate means.

Multiple myeloma may cause ciliary body cysts, which may lead to secondary glaucoma arising from lens dislocation or anterior displacement of the iris root.

Large cell lymphoma may mimic uveitis and may infiltrate the uveal tract, leading to secondary angle closure.

Juvenile xanthogranuloma is a benign histiocytic tumor affecting the skin and eye in young children.

• A salmon colored iris tumor is associated with spontaneous hyphema in children .

• Radiation therapy to the iris tissue has helped to resolve the iris tumor and glaucoma.

DIFFERENTIAL DIAGNOSES1. Glaucoma, Angle Closure, Acute2. Primary Angle-Closure Glaucoma3. Hyphema Glaucoma4. Lens-Particle Glaucoma5. Neovascular Glaucoma6. Pigmentary Glaucoma7. Primary Open-Angle Glaucoma8. Pseudo exfoliation Glaucoma9. Unilateral Glaucoma10. Uveitic Glaucoma

Leukemia Involvement of the eye can occur in just

under one-third of cases of systemic leukemia. Secondary glaucoma is generally caused by AC angle obstruction from leukemic cells

Retinoblastoma Retinoblastoma is the most common

primary intraocular tumor in children and most commonly presents with strabismus and leukocoria. Patients also rarely can have a red, painful eye either from inflammation or elevated IOP.

DIAGNOSTIC PROCEDURES If there is still uncertainty with the diagnosis

after a full history, physical exam and imaging then diagnostic sampling of the lesion can be performed for most tumors.

The use of fine needle aspiration biopsy with either a 25-guage needle or vitrector can be performed .

PROCEDURES For tissue diagnosis, fine-needle biopsy,

aqueous aspiration, or excisional biopsy is needed.

Diagnosis of iris nevus is aided by fluorescein angiography of iris, aqueous aspiration, or biopsy.

MANAGEMENT

MANAGEMENT For intraocular tumors with secondary

glaucoma elimination of the viable tumor cells is of primary importance.

Control of IOP control is secondary and can be done either medically or surgically.

MEDICAL THERAPY Treatment of the secondary glaucoma should

begin with topical eye drops (alpha-agonists, beta-blockers and carbonic anhydrase inhibitors) which decrease aqueous humor production.

If the pressure remains uncontrolled on topical medication then oral hypotensive agents like acetazolamide or methazolamide should be tried.

For metastases with multiple lesions in the eye, systemically chemotherapy can play a large role. In eyes that have poor visual potential and elevated pressure, treatment for the secondary glaucoma should only be given if pain is present.

MEDICAL CARE Glaucoma management itself begins with medical

therapy, concurrent with treatment of the intraocular tumor through surgery, radiation, chemotherapy, or a combination of these treatments.

1. Standard methods of IOP control should be used, although success rates with these topical medications will necessarily be low.

2. Anti-vascular endothelial growth factor (anti-VEGF) therapy may be helpful in those cases where neovascularization plays a role in the pathogenesis of the glaucoma.

3. In systemic lymphoma, leukemia, and metastatic malignancies, treatment will often include systemic chemotherapy and radiation, with current regimens favoring the use of chemotherapy first.

SURGERY Sometimes treatment of the underlying

tumors with plaque brachytherapy, external beam radiation, chemotherapy or radiation can improve the IOP.

For certain tumors like large uveal melanomas, retinoblastoma or if the eye is painful with no visual potential then primary enucleation may be the appropriate option.

SURGICAL CARE Surgical options to control intraocular pressure

must be tempered by the need for preventing extraocular tumor spread.For smaller tumors, observation is warranted

until growth is documented.Iridectomy are options for removing smaller

tumors.For anterior tumors, argon laser to tumor-free

areas is an option.More posterior tumors may require local

resection, photocoagulation, or episcleral radiopaque therapy.

Enucleation is also an option.

For melanocytoma, laser or surgical excision of the lesion may decrease the pigment load and decrease the IOP.

Glaucoma usually is associated with advanced stages of Retinoblastoma, and enucleation may need to be discussed.

Any surgical intervention must be tempered by the risk of extra ocular spread.

Blind eyes should not undergo incisional glaucoma surgery because of the risk of spreading the tumor to outside the globe.

PROGNOSIS With early detection, the outlook is

improved. The prognosis for the patient depends

upon the type of tumor, the amount of involvement within the eye, as well as the treatment received.

The primary goal for any treatment is to control the tumor first and then control the IOP.

Management of any intraocular tumor must be done concurrently with an oncologist to account for systemic disease.

ComplicationsEven with early detection and aggressive therapy for intraocular tumors, loss of the eye or death can occur.A significant number of patients will develop side effects from treatment of the original tumor with brachytherapy which can lead to neovascularization and secondary angle-closure glaucoma.

ConsultationsGlaucoma specialist or oncologist

Patient EducationFollow-up care is important.

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