Medical Retina: Treating Retinal Disease Without Surgery

At Kyushu University’s graduate school I majored in immunology and earned my degree (Medical Institute of Bioregulation).
It became an opportunity to think about retinal disease from the perspective of immunology.

TOC

Medical retina (care of retinal diseases without surgery)

Long-established treatments for retinal disease: steroids and retinal photocoagulation

○ Complications of diabetes

Diabetic macular edema (DME)
Proliferative diabetic retinopathy (PDR)

* Fine blood vessels are damaged by diabetes over a long period, and blood circulation (blood flow) in the retina worsens.

Severity: DME < PDR.

○ Diseases in which retinal blood vessels become blocked

Branch retinal vein occlusion (BRVO)
Central retinal vein occlusion (CRVO)

* When retinal blood vessels suddenly become blocked, retinal blood circulation (blood flow) becomes extremely poor.

Severity: BRVO < CRVO.

Hypertension, arteriosclerosis, diabetes and the like are risk factors.

✔︎ A retina with poor circulation (ischemia): the “root of all evil”
→ It becomes inflamed, and the proteins it produces (cytokines) accumulate inside the eye.

In treating these retinal diseases, we sometimes perform a sub-Tenon triamcinolone acetonide injection (STTA).
This is a treatment in which a steroid suspension is deposited behind the eyeball.
The effect lasts for 2–3 months and mainly improves retinal edema (accumulation of fluid) caused by inflammation.

“Using steroids to suppress inflammation”
has been done for a long time, but it is still an important treatment today.
For retina judged to be ischemic, we perform sufficient retinal photocoagulation (retinal laser).
This relatively reduces the area that causes inflammation, that is, the ischemic retina.

The types and amounts of the proteins (cytokines) that cause trouble inside the eye followed a pattern

At that time, many vitrectomies were being performed at the Kyushu University Hospital Department of Ophthalmology, and we set out to analyze the vitreous fluid.

In addition to the retinal diseases listed above,

○ Diseases in which a hole forms in the retina and it detaches
Rhegmatogenous retinal detachment (RRD)

* When the detachment reaches the macula (the important part for seeing), it leads to blindness.
* Increased floaters (the sense of specks drifting in view) is often the symptom you notice.
* Prompt surgical treatment is required.

Vitrectomy is
surgery that removes the vitreous, the gel inside the eye, and replaces it with fluid.

At the same time as relieving the harmful pull of the vitreous on the retina (release of vitreous traction),
it also greatly reduces the proteins (inflammatory cytokines) that have accumulated inside the eye.

After obtaining approval from the ethics committee,
we analyzed many vitreous samples stored frozen at −80 °C,
and found that there are inflammatory cytokines (proteins) that commonly rise.

• Interleukin-6 (IL-6)
• Interleukin-8 (IL-8)
• Monocyte chemoattractant protein-1 (MCP-1)
• Vascular endothelial growth factor (VEGF)

Higher concentrations of inflammatory cytokines make retinal and vitreous disease more active:
the results also suggested that inflammation becomes stronger as the area of retina with poor blood flow (ischemia) becomes wider.

I remember being surprised at the time by the fact that strong inflammation occurs inside an eye with a detached retina.

We statistically analyzed the results obtained from 428 samples and published them.

Thank you to the doctors who cooperated.

Vitreoretinal immunity (immunity in retinal and vitreous disease)

The results supported the finding that suppressing inflammation with steroids was effective for retinal disease.

Treatment that suppresses vascular endothelial growth factor (VEGF)

Steroids suppress inflammation overall, but they have side effects.
(cataract, rise in eye pressure, steroid glaucoma, infection, etc.)

Researchers around the world have been testing whether other factors might work.

In 1994, Dr. Aiello of Harvard University in the United States
reported that “VEGF concentrations are elevated in diabetic retinopathy and other retinal diseases.”

Aiello, L., et al. (1994). Vascular Endothelial Growth Factor in Ocular Fluid of Patients with Diabetic Retinopathy and Other Retinal Disorders The New England Journal of Medicine 331(22), 1480-1487. https://dx.doi.org/10.1056/nejm199412013312203

Research then advanced worldwide, and countless papers have been published on VEGF.

Treatment that reduces VEGF inside the eye with drugs:
When anti-VEGF antibodies came into use in 2008, I remember being amazed by the dramatic effect.

Today, injecting
• Lucentis®^®(Novartis Pharma)
• Eylea®^®(Santen Pharmaceutical)
• Beovu®^®(Novartis Pharma)

directly into the eye (into the vitreous) is the method used.

Advances in diagnostic imaging:
Visualizing retinal blood vessels without contrast dye / assessing the choroid, the layer deeper than the retina

Added August 29, 2021: the following are now available:

» Advances in retinal imaging: ultra-widefield fundus imaging

In the care of retinal disease and uveitis, we have performed fluorescein angiography (FAG).

It carries a risk of shock from contrast-dye allergy, and it seems that fewer private clinics perform it.

OCT angiography (OCTA)
is what we use in practice.

There is no risk from contrast dye.

In addition to the retinal diseases above,

○ Age-related damage to the center of the retina (macula)
Age-related macular degeneration (AMD)

○ Damage to the center of the retina (macula) associated with high myopia
Myopic macular degeneration; myopic maculopathy

○ Fluid accumulating in the center of the retina (macula)
Central serous chorioretinopathy (CSC)

○ The choroid becomes thick, and choroidal neovascularization develops
Pachychoroid neovasculopathy (PNV): * The concept overlaps with each of the diseases above.

For the retinal diseases above,

OCT angiography visualizes:
• the state of ischemic retina
• the state of choroidal neovascularization
• the state of retinal neovascularization　
• the state of the macular avascular zone

To assess the choroid, the layer deeper than the retina,

we also use the enhanced depth imaging OCT (EDI-OCT)
mode.

• choroidal thickness
• state of the choroidal vessels

and similar information can be obtained.

OCTA and EDI-OCT are also useful in the care of uveitis.

After about two years of use since opening the clinic,
it makes me feel the pace of the times that even a private clinic can visualize the state of the vessels and the choroid so clearly.

* In some cases, a precise examination with contrast dye is needed.

Medical retina (care of retinal diseases without surgery): our role

With the dramatic development of drug treatment and diagnostic imaging,
retinal diseases that can be treated without surgery have increased greatly compared with before.

“Medical retina” is a term set against “surgical retina” (surgical treatment of the retina).
I feel it is a term we have started to hear in about the past ten years.

What we do in Takatori is
○ Early detection and follow-up of retinal disease using diagnostic imaging
○ Treatment without surgery
○ Creating an environment where you can “visit any time” and “ask questions until you understand,” so as to respond to patients’ concerns

These are our roles.

Depending on the indication, we refer you to doctors who specialize in eye surgery.
We also often provide “co-management.”

The most important thing is not to miss the right time.

We provide care with the help of connections in the Kyushu University ophthalmology department and many other doctors.
Thank you, as always.

» Ophthalmic “preventive medicine”: care tailored to the community (update)

» OCT angiography (optical coherence tomography angiography)

» Why we use laser treatment on the fundus and injections into the eye

» The possibility that cytokine (IL-6) biologics may work against coronavirus infection

» Diabetes and the eyes