Eye conditions: Retinal disorders: Pathology review

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Case study0:00–1:01

At the ophthalmology clinic, 71-year-old Zoe comes in. She says that about 4 hours ago, she experienced a sudden flash of light followed by many floaters in her right eye.
Her visual disturbances have since progressed to a peripheral loss of vision, and it’s spreading to the rest of her visual field.
Next to her, an 8-month-old male infant named Nirban, is brought in by his father, who is worried because he noticed that Nirban’s eyes appear white in their family pictures.
Ophthalmologic examination reveals the absence of red reflex on both eyes. On further questioning, the father tells you that as a child, he had to have his left eye enucleated or removed, but he is unsure as to the exact reason why.Based on the initial presentation, both Zoe and Nirban have some form of retinal disorder.
But first, a bit of physiology. If we zoom into the wall of the eye, it is made up of three major layers.

Physiology1:01–1:48

There's a fibrous outer layer, which contains the cornea and sclera, and helps shield excess light. The middle vascular layer is called uvea and consists of the iris, pupil, choroid, and ciliary body.
Finally, the neural layer consists of the retina, with its own outer pigmented layer, and an inner neural layer that’s composed of photoreceptor cells, which convert light into neural signals that travel via the optic nerve to the brain for visual processing.
Okay, let’s start with age-related macular degeneration or ARMD for short. This refers to an acquired degeneration of the macula, which is the central area of the retina.

Macular degeneration1:48–4:11

It can be divided into dry or non-exudative ARMD, which accounts for the vast majority of cases, and wet or exudative ARMD.
Dry ARMD is characterized by yellowish extracellular deposits of waste materials that build up between the Bruch membrane and the retinal pigment epithelium.
For your test, remember that these deposits are often known as Drusen. On the other hand, in wet ARMD, there is abnormal neovascularization, meaning that abnormal blood vessels grow from the choroid behind the retina and can leak intravascular fluid or blood.
In terms of symptoms, dry ARMD usually presents with gradual vision problems, such as metamorphopsia, which is a type of distortion where linear objects appear curved or discontinuous, as well as scotomas or missing areas of vision, and eventually it can lead to central vision loss.
In contrast, wet ARMD causes rapid central vision loss over a few weeks or months. Ultimately, individuals with ARMD can become legally blind, even though their peripheral vision remains intact.
Diagnosis is based on fundoscopy, and treatment focuses on slowing vision loss. For dry ARMD, multivitamin and antioxidant supplements have been shown to help, while wet ARMD can be treated with injections of anti-vascular endothelial growth factors or anti-VEGF for short, like bevacizumab or ranibizumab, which inhibit neovascularization.Next, there is diabetic retinopathy, which is retinal damage resulting from long-standing and poorly controlled hyperglycemia in people with diabetes mellitus.

Diabetic retinopathy4:11–6:00

It can be broken down into nonproliferative diabetic retinopathy, where damaged capillaries leak blood into the retina, and proliferative, where chronic hypoxia results in neovascularization, or the formation of new blood vessels that are fragile and can break, bleeding into and damaging the retina.
For your tests, it’s important to remember that diabetic retinopathy is usually asymptomatic until late stages when it causes painless visual impairment that can progress to blindness.
Diagnosis is made with fundoscopic examination, which in the case of nonproliferative retinopathy, reveals microaneurysms, along with the high-yield cotton-wool spots, which are fluffy white patches on the retina.
Now, in addition to these findings, proliferative retinopathy also shows neovascularization. Treatment of non-proliferative diabetic retinopathy relies on blood glucose control, while proliferative diabetic retinopathy can be managed with anti-VEGF injections, peripheral retinal photocoagulation or surgery.
Bear in mind that both nonproliferative and proliferative diabetic retinopathy can be prevented by keeping blood sugar under control.Similarly, there is hypertensive retinopathy, which refers to retinal damage from chronic, uncontrolled hypertension.

Hypertensive retinopathy6:00–7:22

For your exams, remember that this is associated with an increased risk of stroke, coronary artery disease, and kidney disease.
Now, only in late stages, hypertensive retinopathy may present with decreased or blurred vision. Fundoscopic examination may reveal microaneurysms and cotton-wool spots.
But what’s even more characteristic is the macular star, which results from the star-like deposition of exudates into the macula, along with flame-shaped retinal hemorrhages, and arteriovenous nicking.
This is seen when an arteriole with a thick arteriosclerotic wall compresses a vein that it happens to cross, so this vein bulges on both sides next to the crossing.
In severe cases, papilledema or swelling of the optic disk can also be seen. Treatment of hypertensive retinopathy requires immediate and long-term control of blood pressure.Moving on to papilledema, which refers to swelling of the optic disc.

Papilledema7:22–8:23

This is classically caused either by severe hypertensive retinopathy, or by increased intracranial pressure due to a space-occupying lesion, such as tumor or hemorrhage.
Symptoms include blurring, flickering or even complete vision loss. For your exams, remember that in the case of increased intracranial pressure, individuals will often experience nausea and vomiting as well.
For diagnosis, fundoscopic examination might reveal an enlarged blind spot and an elevated optic disc with blurred margins.
Treatment focuses on managing the primary cause. If a reduction of intracranial pressure is needed, diuretics and antihypertensives are commonly used.Next, retinal vein occlusion refers to the compression of the central retinal vein or one of its branches due to a thrombus, a narrow vein, or from an atherosclerotic artery crossing it.

Retinal vein occlusion8:23–9:25

This manifests as an acute monocular vision loss. For diagnosis, look for a history of cardiovascular risk factors, such as diabetes mellitus and hypertension, or hypercoagulable states like polycythemia vera.
For diagnosis, fundoscopic examination may reveal optic disc swelling, retinal hemorrhages, and dilated veins that give a characteristic “blood and thunder appearance”.
Edema in affected areas can also be seen. Treatment can include laser photocoagulation, and steroid or anti-VEGF injections.Now, don’t confuse retinal vein occlusion with central retinal artery occlusion, which also results in acute monocular vision loss.

Artery occlusion9:25–10:53

This can be caused by an embolism resulting from atrial fibrillation, cardiac vegetations or a patent foramen ovale, but might be also due to thrombosis of the retinal artery, usually as a result of atherosclerosis.
On fundoscopy, the retina appears cloudy with attenuated vessels and the characteristic "cherry-red" spot in the fovea or center of macula.
For your exams, note that this is seen because the macula receives its blood supply from the choroid, which remains unaffected, while the surrounding retina is pale and ischemic due to the retinal artery occlusion.
Treatment may include hyperbaric oxygen therapy, which involves the inhalation of 100% oxygen at a pressure that’s higher than the atmospheric pressure.
The purpose of this is to raise the amount of oxygen delivered to the ischemic retinal tissue. Finally, to prevent further embolism, it’s also important to find the embolic source.Next, retinal detachment occurs when the neurosensory layer of the retina is separated from the underlying retinal pigment epithelium, resulting in degeneration of the photoreceptors and, eventually, vision loss.

Retinal detachment10:53–13:02

The most frequent cause are retinal breaks, which can be secondary to head trauma or vitreous degeneration, which is a natural process that occurs with aging, where the vitreous humor changes from being a thick gel to a watery fluid.
Significant vitreous degeneration can lead to a posterior vitreous detachment, which in turn causes traction on the retina and, potentially, a retinal tear.
The liquefied vitreous can then seep through the tear and under the retina, causing it to detach. Another high-yield fact is that retinal breaks are also much more common in those with high myopia.
Less frequently, retinal detachment can occur without any tears. This is typically the result of traction on the newly formed blood vessels in proliferative diabetic retinopathy or inflammatory effusions.
The classic exam vignette will present someone with light flashes or floaters described as fine dots, veils, cobwebs, clouds, or strings, followed by sudden visual field loss in the affected eye.
This typically begins in the periphery, and progresses toward the central visual axis over hours to weeks like a “curtain drawn down”.
Diagnosis is based on fundoscopic examination, which may visualize crinkling of retinal tissue or changes in blood vessel direction.
For your test, remember that retinal detachment is an emergency and requires surgery to restore sensory function.Next is retinitis pigmentosa.

Retinitis pigmentosa13:02–13:43

This is a hereditary degeneration of the retina that results in painless, progressive vision loss. What’s high-yield to know is that it starts with night blindness and peripheral vision loss and, in late stages, goes on to affect central vision.
Retinitis pigmentosa takes its name from the fundoscopic exam showing a pattern of bone spicule-shaped dark spots and blotches that are visible around the macula of the retina.
Unfortunately, there is no effective treatment.The last retinal disorder is retinoblastoma. This is a relatively common tumor in childhood caused by the mutation of both alleles of the retinoblastoma or RB1 gene on chromosome 13.

Retinoblastoma13:43–16:56

Now, retinoblastomas can be hereditary, in which case the individual usually inherits a mutation in one of the alleles of the RB1 gene.
If, for some reason, a random mutation occurs in the second allele of the RB1, that leads to the development of retinoblastoma.
This is known as the two-hit hypothesis. For your test, keep in mind that hereditary retinoblastomas are typically bilateral and are associated with an increased risk of developing other malignancies like osteosarcoma, soft tissue sarcoma and malignant melanoma.
Another high-yield fact is that an individual with hereditary retinoblastoma has a 50% chance of passing on the mutated allele to their child.
Now, there are also sporadic retinoblastomas, which occur when two spontaneous mutations affect both RB1 alleles. For your exams, remember that sporadic retinoblastomas tend to be unilateral.
Now, in terms of symptoms, what’s especially high-yield is that retinoblastoma typically presents with leukocoria or “white pupil.” So when flashy photography of the person is taken, instead of the red eye effect, they’ll have white pupils.
This is particularly noticeable for unilateral cases since in the normal eye, the light will reflect from the fundus and appear red, but the tumor that grows on the fundus will block light so it appears white.
Remember that another cause of leukocoria is congenital cataract. The tumor can also cause eye pain if large enough.
Now, if the tumor metastasizes, it can also present with anorexia or lack of appetite, weight loss, vomiting, headaches, or neurologic impairment.
Diagnosis of retinoblastoma begins with a red reflex test which functions similarly to flash photography. Light is directed from an ophthalmoscope through the eye and then reflected back from the retina and appears red..
And since the retinoblastoma blocks the light, the red reflex will be absent in the affected eye. This is followed by a fundoscopy examination to confirm the diagnosis of retinoblastoma and to determine its exact location and extent of involvement.
Definitive treatment consists of enucleation or complete removal of the eyeball.All right, as a quick recap, retinal conditions include age-related macular degeneration, which is most often dry or nonexudative, and rarely wet or exudative.

Review16:56–18:25

Diabetic retinopathy results from long-standing and poorly controlled diabetes mellitus, and can be proliferative or nonproliferative.
Hypertensive retinopathy results from chronic, uncontrolled hypertension. Papilledema refers to optic disc swelling due to hypertensive retinopathy or increased intracranial pressure.
Retinal vein occlusion is associated with a thrombus or an atherosclerotic artery compressing the retinal vein or a branch, while central retinal artery occlusion is due to embolism or atherosclerosis.
Retinal detachment is usually due to retinal tears, but can be also caused by diabetic traction or inflammatory effusions and is a surgical emergency.
Retinitis pigmentosa is an inherited, progressive retinal degeneration. Finally, retinoblastoma can be hereditary or sporadic, and causes leukocoria and absent red reflex.Okay, back to our cases.

Summary18:25–19:14

71-year-old Zoe came in, complaining of an acute case of vision loss that’s described as the ‘curtain being drawn down” in her right eye.
This was preceded by flashes and floaters. This is classic for retinal detachment, which was then confirmed with fundoscopy and treated with surgery in an emergency setting.
On the other hand, Nirban, the 8-month-old infant presented with bilateral leukocoria. This, along with the absence of red reflex and the possible family history, suggests bilateral, hereditary retinoblastoma.
Diagnosis was confirmed with fundoscopy and treatment involved enucleation.