This condition is often associated with diabetes in advanced proliferative diabetic retinopathy. Other conditions causing rubeosis iridis include central retinal vein occlusion, ocular ischemic syndrome, and chronic retinal detachment.

Rubeosis iridis, also called neovascularization of the iris (NVI), is a medical condition of the iris of the eye in which new abnormal blood vessels (formed by neovascularization) are found on the surface of the iris.

Vitreous hemorrhage is the extravasation, or leakage, of blood into the areas in and around the vitreous humor of the eye. The vitreous humor is the clear gel that fills the space between the lens and the retina of the eye. A variety of conditions can result in blood leaking into the vitreous humor, which can cause impaired vision, floaters, and photopsia.

The most common cause found in adults is diabetic retinopathy. Abnormal blood vessels can form in the back of the eye of a person with diabetes. These new blood vessels are weaker and prone to breaking and causing hemorrhage. Diabetic retinopathy accounts for 31.5-54% of all cases of vitreous hemorrhage in adults in the United States.

Those with ocular ischemic syndrome are typically between the ages of 50 and 80 (patients over 65) ; twice as many men as women are affected. More than 90% of those presenting with the condition have vision loss. Patients may report a dull, radiating ache over the eye and eyebrow. Those with ocular ischemic syndrome may also present with a history of other systemic diseases including arterial hypertension, diabetes mellitus, coronary artery disease, previous stroke, and hemodialysis.

The condition presents with visual loss secondary to hypoperfusion of the eye structures. The patient presents with intractable pain or ocular angina. On dilated examination, there may be blot retinal hemorrhages along with dilated and beaded retinal veins. The ocular perfusion pressure is decreased.

The corneal layers show edema and striae. There is mild anterior uveitis. A cherry-red spot may be seen in the macula, along with cotton-wool spots elsewhere, due to retinal nerve fiber layer hemorrhages. The retinal arteries may show spontaneous pulsations.

As of 2012, the rate of hyphemas in the United States are about 20 cases per 100,000 people annually.

Hyphema (or hyphaema, see spelling differences) is blood in the front (anterior) chamber of the eye. It may appear as a reddish tinge, or it may appear as a small pool of blood at the bottom of the iris or in the cornea.

If carotid occlusive disease results in ophthalmic artery occlusion, general ocular ischemia may result in retinal neovascularization, rubeosis iridis, cells and flare, iris necrosis, and cataract. The condition leads to neovascularization in various eye tissues due to the ischemia. The eye pressure may become high due to associated neovascular glaucoma. An ischemic optic neuropathy may eventually occur.

Heterochromia is classified primarily by onset: as either genetic or acquired.

Although a distinction is frequently made between heterochromia that affects an eye completely or only partially (segmental heterochromia), it is often classified as either genetic (due to mosaicism or congenital) or acquired, with mention as to whether the affected iris or portion of the iris is darker or lighter. Most cases of heterochromia are hereditary, caused by certain diseases and syndromes. Sometimes one eye may change color following disease or injury.

Acquired heterochromia is usually due to injury, inflammation, the use of certain eyedrops that damages the iris, or tumors.

Juvenile xanthogranuloma (JXG) is a form of histiocytosis, classified as "non-Langerhans cell histiocytosis", or more specifically, "type 2".

It is a rare skin disorder that primarily affects children under one year of age but can also be found in older children and adults. It was first described in 1905 by Adamson. In 5% to 17% of people, the disorder is present at birth, but the median age of onset is two years. JXG is a benign idiopathic cutaneous granulomatous tumor and the most common form of non-Langerhans cell histiocytosis (non-LHC). The lesions appear as orange-red macules or papules and are usually located on the face, neck, and upper trunk. They may also appear at the groin, scrotum, penis, clitoris, toenail, palms, soles, lips, lungs, bone, heart, and gastrointestinal tract more rarely. JXG usually manifests with multiple lesions on the head and neck in cases with children under six months of age. The condition usually resolves spontaneously over one to five years. A biopsy of the lesion is critical to confirm the diagnosis.

Ocular JXG manifests in up to 10% of people with JXG and may affect their vision. The presence of JXG in the eye can cause spontaneous hyphema, secondary glaucoma or even blindness. It is most often seen in the iris but may be found on the eyelid, corneoscleral limbus, conjunctiva, orbit, retina, choroid, disc, or optic nerve. Of patients with ocular JXG, 92% are younger than the age of two. Although cutaneous JXG usually disappear spontaneously, ocular lesions rarely improve spontaneously and require treatment. Treatments that have been used include surgical excision, intralesional steroid injection, cryotherapy, and low dose radiotherapy. In the case of a resistant or reoccurring lesion, chemotherapy has been used as a treatment. Ocular JXG is usually unilateral and presents with a tumor, a red eye with signs of uveitis, unilateral glaucoma, spontaneous hyphema or heterochromia iridis. Diagnosing and treating the patient as early as possible contributes to the most positive visual outcome.

Histiocytic disorders like JXG are identified by the cells that make them up. Immunohistochemical analysis is used to discern the immunoreactivity to certain antibodies in these analyses. JXG is a non-LHC disorder which is a varied group of disorders defined by the accumulation of histiocytes that do not meet criteria to be diagnosed as Langerhans cells. JXG is not metastatic and may be present with lipid deposits. JXG is often accompanied with other disorders such as neurofibromatosis type one and juvenile chronic myelogenous leukemia. Juvenile variety xantogranuloma can be distinguished from xanthoma by the spread of the lesion and the lack of lipid abnormalities. Other similar diagnoses include molluscum contagiosum, hemangioma and neurofibroma.

The presentation of this condition includes a characteristic facies. The cardiac manifestations include patent ductus arteriosus, congenital hypertrophy of the left ventricle, and pericardial effusions.

Neurodevelopmental outcome appears normal, but obsessive traits and anxiety have been reported. It may also be associated with recurrent infections with low immunoglobulin levels and gastric bleeding, and additional possible associations include lymphoedema and heterochromia iridis.

Cantú syndrome (hypertrychotic osteochondrodysplasia) is a rare condition characterized by hypertrichosis, osteochondrodysplasia, and cardiomegaly. Less than 50 cases have been described in the literature; they are associated with a mutation in the "ABCC9"-gene that codes for the ABCC9-protein.

In the beginning, medical officials defined ABCD syndrome by the four key characteristics of the syndrome. In the first case study of the Kurdish girl, researches described her as having "albinism and a black lock at the right temporo-occipital region along Blaschko lines, her eyelashes and brows were white, the irises in her eyes appeared to be blue, she had spots of retinal depigmentation, and she did not react to noise." The albinism is interesting in this diagnosis because the skin of an affected individual is albino pale besides the brown patches of mispigmented skin. The "black locks" described and seen in clinical pictures of the infants are thick patches of black hair above the ears that form a half circle reaching to the other ear to make a crest shape.

As identified in this first case study and stated in a dictionary of dermatologic syndromes, ABCD syndrome has many notable features, including "snow white hair in patches, distinct black locks of hair, skin white except brown macules, deafness, irises gray to blue, nystagmus, photophobia, poor visual activity, normal melanocytes in pigmented hair and skin, and absent melanocytes in areas of leukoderma." Individuals have the blue/gray irises typical of people affected by blindness. The C of ABCD syndrome is what distinguishes this genetic disorder from BADS and it involves cell migration disorder of the neurocytes of the gut. This characteristic occurs when nerve cells do not function correctly in the gut, which results in aganglionosis: The intestines’ failure to move food along the digestive tract. Deafness or being unresponsive to noise due to very low quality of hearing was reported in every case of ABCD syndrome. The characteristics of ABCD syndrome are clearly evident in an inflicted individual.

No longer considered a separate syndrome, ABCD syndrome is today considered to be a variation of Shah-Waardenburg type IV. Waardenburg syndrome (WS) is described as "the combination of sensorineural hearing loss, hypopigmentation of skin and hair, and pigmentary disturbances of the irides." Hearing loss and deafness, skin mispigmentation and albinism, and pigmentary changes in irises are the similarities between WS and ABCD. According to a dictionary of dermatologic syndromes, Waardenburg syndrome has many notable features, including "depigmentation of hair and skin – white forelock and premature graying of hair, confluent thick eyebrows, heterochromic irides or hypopigmentation of iris, laterally displaced inner canthi, congenital sensorineural deafness, broad nasal root, autosomal dominant disorder, and other associated findings, including black forelocks."

ABCD syndrome is the acronym for albinism, black lock, cell migration disorder of the neurocytes of the gut, and sensorineural deafness. It has been found to be caused by mutation in the endothelin B receptor gene (EDNRB).