The Pathology:

It is a form of cancer characterized by the growth of mutated cells within the bulbus oculi, better known as the eyeball, alongside the parts surrounding the eyeball itself; such as the lacrimal gland (responsible for producing tears) and even the eyelids.

Eye cancer is generally categorized into primary and secondary cancer—the former branches off into several other subtypes, while the latter refers to cancer that has spread to the eyes from other parts of the body, commonly the lungs and breasts. This form of cancer renders the eyes unable to function to the fullest. Simple tasks cannot be performed without additional hindrance. Patients find it difficult to see clearly, experiencing changes such as blurred or doubled vision, floaters/lines in vision, flashes of light, or a constantly growing blind spot in the eye.

• Forms of eye cancer that involve tumor growth affect the tear ducts which may lead to individuals experiencing epiphora (watery eyes) and a constant dull ache in the regions surrounding the affected eye. Fig: The image above represents the growth of a malignant tumor in the back. Of an eyelid, picturing the difference between the regular anatomy of the human eye versus an affected one.
• Ocular oncology is the branch of medicine that specifically concerns this form of cancer. The primary cause behind the development of this particular type of cancer is difficult to trace. However, oncologists argue that constant exposure to Ultraviolet sun rays can be a major facilitator of malignant tumor development.

Statistics:

As for India specifically, it is difficult to discern data from specific regions due to the lack of proper diagnosis in rural areas. However, roughly 10,000 new cases of eye cancer specifically are seen in the country each year. India in particular, has a high incidence of tumors within the eye, and according to a few statements, it hosts nearly 30% of global eye cancer cases, with about 65% of tumors as benign, ~32% as malignant, and 3% as pre-malignant. Carcinomas and retinoblastoma are the dominating subtypes in the region.

• In recent years, the highest incidence of eye cancer has been observed in North America and Australia, when connected to the risk factors, exhibit how individuals of caucasian descent and exposure to high amounts of UV radiation are associated with an increased risk to developing this particular form of cancer. The Sub-Saharan African region also reflects a high incidence, likely due to its distance from the equator and exposure to UV light.
• Approximately 47,000 new cases of eye cancer emerged globally in the year 2020. Global mortality due to conditions that fall under this term rose to about 8,202 deaths in a single year—almost 0.8 per 100,000 people.

Subtypes of this form of cancer:

When a patient is said to have ‘eye cancer’, it is important to know that the term is broad and can be used to describe many organs/separate tissues around the eye affected by cancer. Cancer can originate both within the eye and outside, ultimately spreading to the eye from other organs, or vice versa.

‘Eye cancer’ is the umbrella term for the following types of cancer: ● Melanoma: the type of cancer that develops in the melanocyte cells, which are essential for the production of melanin, which provides humans with the pigment for their skin, hair, and eye color. Melanoma may develop from an irregularly shaped mark/mole on the skin and then expand into other parts of the body.

1. Ocular melanoma is the term used to define melanomas that have either originated within the eye or have spread to the eye, thus counting as eye cancer in both situations.
2. Subcategories include: uveal melanoma (begins within the iris),
3. Ciliary body melanoma (muscle fibre by the lens of the eye)
4. Choroidal melanoma - develops in the layer of blood vessels behind the eye
5. Eyelid melanoma - skin cancer on top of the eyelids
6. Orbital melanoma - a cancer that develops around the bone structure of the eye socket
7. Conjunctival melanoma - occurs in the conjunctiva, which is responsible for providing the eye with lubrication by producing tears and mucus.

● Retinoblasma: a malignant tumor of the retina (the black circle within the iris) observed primarily in younger children. Permanent blindness/inability to see from the affected eye is typically common in survivors. ● Carcinomas: A cancer that forms in the epithelial tissues surrounding the eyes. These tissues are responsible for forming a protective layer that shields the tissues that lie underneath from any external damage. Carcinoma affects the eyes generally in two distinct ways, namely Basal Cell carcinoma (BCC), which is the most common eyelid cancer, generally treatable; and Squamous Cell carcinoma (SCC), which is another form of skin cancer of the eyelid/conjunctiva, but is considered more aggressive and complex to treat when compared with BCC.

Location:

• Eye cancer refers to primary cancer (one that begins within the eye) and secondary cancer (one that has spread to the eyes but originated in a separate organ).
• The specific parts of the eye that are affected include the iris (the colored part within the eye), the ciliary body (a ‘ring of tissue’ within the eye), the choroid (the vascular layer within the eyeball, in ‘between the retina and the sclera’), the sclera (the white part of the eyeball), and the skin in the eyelids—both upper and lower.

Stages:

It is considered to have four main stages (I-IV).

The higher numbers indicate that the person has an advanced stage of cancer, meaning that it has likely spread across different organs throughout the body.

The Collaborative Ocular Melanoma Study (COMS) classification also classifies eye cancer based on the size of the tumour, if there is one; the size of the tumour is directly proportional to the severity of the case. Fig: A visual representation of how eye(-lid) cancer stages manifest physically. Fig: The image above is an example of the progression/different stages of uveal melanoma in different patients. The development of eye cancer is often evident to even those without trained eyes. Melanoma, for instance, grows at the surface of the skin and therefore, is visible.

Symptoms:

Eye cancer may reflect through multiple major and even minor physical symptoms, which is why it is crucial to recognise them to diagnose the condition on time.

• If someone were to observe a lump around either their upper or lower eyelid, dark spots within their iris that obstruct their vision and individuals may even experience sudden flashes of light and consequently, light sensitivity.
• A bulging eye may be observed in more extreme cases, indicating a tumour has already developed. All patients would likely experience redness within the eye and almost constant pain.

Risk factors and causes:

There is a varied range of risk factors that can increase an individual’s chances of developing any form of eye cancer; these include:

1. Being of caucasian descent: Individuals of caucasian descent (i.e., individuals with light skin, fair complexion, and even light eyes) are deemed more likely to have this form of cancer. Less melanin in the iris specifically reduces natural protection from ultraviolet radiation. Individuals who often get sunburnt or freckle quickly are considered to have a higher chance of developing melanoma.
2. Moles within the eye: Individuals with moles within the eye (often visible in the sclera/ ‘white regions’ of the eye) have a higher chance of developing melanoma within the eye.
3. Genetics: Inheritable genetic mutations are often cited as a major risk factor for cancer in general. Mutations in the gene can often lead to uncontrolled growth of cells that may lead to the formation of cancer, most commonly a tumour. Genetic mutations such as GNA11 or GNAQ for individuals with eye melanoma, and mutations of the BAP1 gene, which increase the risk of malignant tumour development.
4. Age: People aged 60 or above comprise the majority of such cases, with only Retinoblasma is a subtype of eye cancer where most cases are observed in children aged 2-3.
5. Exposure to Ultraviolet radiation: Constant, direct exposure to Ultraviolet rays not only damages vision in general, but is also capable of mutating/damaging DNA leading to rare eye cancers such as uveal melanoma.
6. HIV: Human immunodeficiency virus, better known as HIV, is a medical condition that weakens the immune system, which may lead to the development of what is known as ‘opportunistic cancer’.

Prevention:

With reference to the risk factors, it is evident that eye cancer is not something that can just be ‘stopped’ from fostering, given the fact that many individuals may have inherited the gene or are of caucasian descent or have medical conditions such as HIV.

1. However, It is recommended to wear UV-protection sunglasses and even wide-rimmed hats in to limit exposure to harmful radiation that may facilitate cancer growth.
2. For Indian citizens in particular, attempting to shield themselves from harsh sunrays is essential due to the geographical location of the country, which exposes them to high amounts of Ultraviolet radiation. A genetic screening may also assist with early detection.

Diagnosis:

Several methods are currently used to diagnose eye cancer effectively. They include the following: ● Eye exam: an ophthalmologist examines both the external and internal structures that comprise/surround the eye. Using eye drops to dilate the pupils to observe the retina (black region within the colored region), uvea (iris), etc. The patient may even be checked for light sensitivity, as eye cancer, even in the early stages, would likely tamper with their visual senses. This is done to gather visual evidence of any abnormalities within the eye. ● Retinal Imaging: Refers to the use of specialised cameras and scanners with the motive of capturing magnified digital images of the back of the eyeball. This can allow tumour detection. ● Ultrasound (UBM): This is another common method of screening in which the high-resolution images captured using ultrasound reveal the size of the tumour (if there is one) and the urgency of the case. ● MRI: Often useful when the previously mentioned conventional methods are ineffective. Although it is recommended not to expose the affected organ to more radiation, an MRI can be effective when prominent images of the tumour are required. ● CT Scan: Not typically used for diagnosing cancer; however, it is often used to check if the cancer has started to reach/is reaching other organs within the body. ● Angiography: This involves injecting a dye into the bloodstream (generally through the arm), which allows the dye to travel to the blood vessels in the eye. This is considered unconventional and is comparatively invasive, but it does allow the ophthalmologist to detect abnormal blood vessels within a tumour. ● Tracing family history: Gathering a history of symptoms and observing patterns (such as the age when cancer began in certain family members may be common and this provides an epidemiological perspective on a patient’s case). Genetic screening is also common nowadays, where individuals with such a family history are scanned for mutations that may lead to a form of eye cancer. ● Biopsy: Involves the use of a tissue sample for a histopathological analysis. It provides a definitive analysis and is thereby one of the most accurate methods of deducing specific factors such as tumour type, grade, and properties, and is particularly useful in cases where imaging/scanning is not producing clear results.

Treatments and Side Effects:

It is popularly recommended to first observe individuals and not attack the tumour in the earliest stages, as that would simply exacerbate complications. There are several different approaches that can be taken to cure eye cancer. And follow-ups to regulate and monitor cancer growth and side effects is suggested. They include:

1. Radiation Therapy- Is applicable for tumours that have not grown significantly. Provides an An effective solution to a situation where an individual would have lost their vision due to surgery. Radiation therapy can still damage smaller, healthy tissues near the eye. People may have to deal with dry eyes, retinal damage, and even partial vision loss.
2. Laser therapy/Thermotherapy- The procedure isn’t particularly invasive and can even help preserve vision if the tumour is smaller. ****While the idea of preserving vision is undoubtedly ideal, The procedure is mostly ineffective when the cancer is larger or more aggressive. Regular scans and imaging may also be required to monitor cancer growth, as switching to a different form of treatment may be more suitable in specific cases.
3. Chemotherapy- anti-cancer drugs are injected systematically into the body through the veins or even locally, near the eye. This has proven to be particularly useful in treating children with Retinoblastoma. Systemic side effects include nausea, hair loss, and a significantly weakened immune system. This treatment also may not work for adults. It is particularly intensive and requires multiple treatment cycles at times. There must be constant monitoring of the patient’s health with checkups and blood tests to ensure side effects are not getting out of hand.
4. Surgery - Can refer to the removal of the tumour only, better known as a local resection, or an Enucleation, removal of the entire eye, is performed if the tumour has grown too large and it is already confirmed that vision cannot be saved. This entails immediate removal of cancerous tissue and reduces the risk of cancer spreading.

The downsides to this treatment include one being the loss of an eye or both in extreme cases. This leads to a change in appearance and can increase a person’s dependence on others a lot more, as it takes time to get accustomed to such a lifestyle. If enucleation is used as the last resort, then a prosthetic eye may be required for the patient. However, personal preference does play a role here. For local resection, the ‘adjustment period’ for vision changes must be monitored.

1. Cryotherapy - More applicable in cases of retinoblastoma. The procedure is minimally invasive and requires no incisions. Healthy tissue can be spared as well. There may be temporary side effects such as vision changes and swelling of the regions surrounding the eye. Treatment would likely take several sessions and be comparatively slow. Albeit rare, there is also a small chance of damaging local healthy tissue. The treatment likely will not help if the cancer has turned metastatic.
2. Immunotherapy/Targeted therapy - As for now, there are not many side effects to this form of treatment, especially when compared to more traditional methods such as chemo, which is likely because immunotherapy is relatively new and methods are still being verified. Therefore, many individuals still do not have access to this form of treatment. It is crucial that patients undergoing any immunotherapy-based treatments consistently follow up with their consultant to monitor for any unanticipated autoimmune reactions to the therapy.

FAQs:

1. What is eye cancer?

• Eye cancer refers to the uncontrollable growth of cells within or in regions surrounding the eye. This can be divided into several subcategories with forms of ocular melanoma being the most common.

1. Is it treatable? If so, how?

• Eye cancer in the early stages is considered treatable. However, especially in Stages III and IV, it becomes increasingly difficult to treat. Options for treatment include surgery, thermotherapy, and chemotherapy ,among others.

1. Can eye cancer come back after treatment?

• Yes, there is a possibility that eye cancer may return after treatment, at times even several years later.

1. How many stages of eye cancer are there?

• There are four stages from each subtype of eye cancer. Ranging from the early stages such as Stage I and later stages such as Stage IV which is when the cancer has become metastatic (spread to other organs).

1. What part of the population is generally affected by this form of cancer?

• Individuals of caucasian descent, prone to freckling, who have moles within their eyes, and are old are usually prone to developing a form of eye cancer. Retinoblastoma is the only exception, where young children are predominantly observed in patient cases.

1. Is the removal of the affected eye unavoidable?

• No. Even though there are several cases where the affected eye had to be removed for full recovery, treatments such as radiation therapy and targeted drugs, can assist in recovery—especially if caught in the earlier stages.

1. How can I support a loved one with eye cancer?

• To support a loved one with eye cancer, one should attempt to stay informed. An individual experiences a major sensory loss as the condition hinders their ability to see which makes day-to-day tasks much more tedious/complex, helping them navigate would ease some of their daily struggles. Attempt to emotionally support them throughout the treatment period.

1. Have any new treatments for this cancer come up?

• Yes, new treatments for eye cancer have come up in recent years. These mostly include immunotherapy drugs such as tebentafusp (for advanced eye melanoma) and ongoing immunotherapy-based studies regarding lymphocytes that could potentially infiltrate tumours and stop them from growing. But most of these methods are still being tested and verified.

1. Is chemotherapy a possibility for patients with eye cancer?

• Yes, chemotherapy is an option for patients suffering from eye cancer, but it is typically not the first treatment of choice. When the cancer becomes metastatic, however, is when chemotherapy is almost inevitable.

1. Can a patient still perform day-to-day tasks with eye cancer?

• A patient’s vision would likely still be impaired/blurred even if they do not experience complete vision loss. This can make daily tasks more challenging, and it is recommended that they have some form of assistance, even though some tasks are considered ‘manageable’.