Laser Treatment of the Fundus and Why We Inject Medication into the Eye

The blood vessels at the back of the eye (retinal vessels) are the only blood vessels in the body that can be seen directly.

A fundus photograph can show

retinal disease, and to some extent also hypertension, arteriosclerosis, and suspected enlargement of the optic disc cup.

(What is flagged at a health checkup is judged from the fundus photograph.)

When you see an eye doctor,

the doctor uses a slit-lamp microscope and a special lens to examine both eyes and capture three-dimensional changes in the retina, vitreous, and optic nerve.

When blood flow to the retina worsens, as in diabetes or retinal vein occlusion (blockage of a blood vessel), inflammation develops in the retina. The inflamed retina releases “inflammatory cytokines.”

Because the inside of the eye is a closed space, the inflammatory cytokines (proteins) that are produced stay inside the eye. (Aqueous humor and vitreous with a high cytokine concentration become more viscous.)

Inflammatory cytokines have actions such as:

• Weakening the walls of blood vessels

• Growing new blood vessels (fragile ones that bleed easily)

• Damaging tissue

• Attracting inflammatory cells

and more.

The reason we treat the retina with a laser is to “thin out” the root of the trouble that produces inflammatory cytokines, that is, the retina with poor blood flow.

In a paper we published in 2009,¹we measured many inflammatory cytokines inside the eyes of 345 patients and analyzed them statistically for each disease.

We concluded that inflammation is involved in many retinal and vitreous diseases, and gave the paper the subtitle “vitreoretinal immunity.”

The results have been used in many lectures and are stillcitedin many countries.

I am grateful to the many teachers who helped me.

Among the inflammatory cytokines, VEGF (vascular endothelial growth factor) is the most important,²and over the past decade, treatment of many retinal diseases, including diabetic macular edema, retinal vein occlusion, age-related macular degeneration, and myopic macular degeneration, has changed greatly: intravitreal injection of anti-VEGF drugs.

The action of IL-6 (interleukin-6) also seems extremely powerful.^3,4I expect that treatments targeting IL-6 will become widespread in ophthalmology in the near future.

[Retinal laser (photocoagulation) treatment / intravitreal injection]

Retina with poor blood flow (→ thin out the retina at the root of the trouble with a laser)

↓　　↑

Inflammation and new blood vessel growth

↓　　↑

Inflammatory cytokines accumulate in the eye (→ suppress the action of the cytokines with a drug)

↓　　↑

The condition of the blood vessels worsens

These treatments intervene in the vicious cycle of the environment inside the eye.

(Reference)
1. Comprehensive analysis of inflammatory immune mediators in vitreoretinal diseases.
Yoshimura T, Sonoda KH, Sugahara M, Mochizuki Y, Enaida H, Oshima Y, Ueno A, Hata Y, Yoshida H, Ishibashi T.
PLoS One. 2009 Dec 4;4(12):e8158
2. VEGF in Signaling and Disease: Beyond Discovery and Development.
Apte RS, Chen DS, Ferrara N.
Cell. 2019 Mar 7;176(6):1248-1264.
3. Roles of IL-6 in Ocular Inflammation: A Review.
Ghasemi H.
Ocul Immunol Inflamm. 2018;26(1):37-50.
4. Involvement of Th17 cells and the effect of anti-IL-6 therapy in autoimmune uveitis.
Yoshimura T, Sonoda KH, Ohguro N, Ohsugi Y, Ishibashi T, Cua DJ, Kobayashi T, Yoshida H, Yoshimura A.
Rheumatology (Oxford). 2009 Apr;48(4):347-54.