MD1843Z - Method for treating severe non-proliferative diabetic retinopathy - Google Patents

Abstract

The invention relates to medicine, namely to ophthalmology, and can be used for treating patients with severe non-proliferative diabetic retinopathy.Summary of the invention consists in performing argon laser therapy in the green range with a wavelength of 532 nm, with beam values: spot diameter of 50…100 µm, current strength of 100…180 mW and duration of action of 0.05…0.09 sec, simultaneously administering alpha-lipoic acid 600 mg is, 1 tablet per day, for 3 months, pentoxifylline retard 400 mg, 1 tablet, 2…3 times a day, for 3 months, a mixture containing thiamine hydrochloride 250 mg, pyridoxine hydrochloride 250 mg and cyanocobalamin 1 mg, one tablet per day, for 2 months.

Description

[0001] The invention relates to medicine, namely to ophthalmology, and can be used for the treatment of patients with severe form of non-proliferative diabetic retinopathy.

[0002] Diabetes is a metabolic disease that affects the entire body and especially the vascular system, including the eyes, giving rise to specific changes, generically called diabetic retinopathy. Diabetic retinopathy is a disease of the blood vessels that supply the retina: they become thin, the walls of the capillaries, which are weakened, allow the plasma to escape from the vessels into the retina, which leads to the appearance of macular edema, in addition, these blood vessels are no longer able to bring the nutrients and oxygen needed by the retina (hypoxia), affecting it even more. The patient notices blurred, unclear vision, spots and flashes, fading of colors and sometimes deformation of objects. The evolution is progressive, and without adequate treatment inevitably leads to blindness.

[0003] Diabetic retinopathy in its early stages has no symptoms (decreased vision, pain, or other signs), therefore, all patients diagnosed with diabetes mellitus must undergo a periodic ophthalmological examination (1...2 times a year), for the early detection of retinal changes. This is important in order to be able to start an effective treatment in a timely manner, when the disease is at its onset. Diabetic retinopathy has 2 distinct forms: the non-proliferative form and the proliferative form, which is characterized by the appearance of new vessels.

[0004] As these lesions accumulate, the earliest signs of diabetic retinal changes, such as vessel distortion and tiny retinal hemorrhages, may appear. When the damage has not progressed to the point where new, abnormal blood vessels develop to try to replace the damaged ones, we call the diabetic condition "nonproliferative diabetic retinopathy."

[0005] Risk factors for the progression of diabetic retinopathy are represented by the type of diabetes mellitus, duration of diabetes, hypertension, dyslipidemia, renal impairment, anemia, smoking, excessive alcohol consumption.

[0006] The best method for preventing blindness is the early diagnosis of diabetic retinopathy and the treatment of vision-threatening lesions before visual acuity is impaired. This goal can only be achieved by annual ophthalmological examination of patients with diabetes. The consultation includes anamnesis with detection of risk factors, determination of visual acuity, intraocular pressure and examination of the fundus of the eye on the dilated pupil using special lenses and digital photography of the retina. This examination is mandatory for any patient from the moment of diagnosis of diabetes and must be repeated annually.

[0007] The severe form of non-proliferative diabetic retinopathy is a more advanced stage, in which hemorrhages and exudates become more numerous and diverse, visual acuity is modified, by affecting the central area of the retina (macular edema). At the same time, the severe form is characterized by a modified vascular density of the retina, namely vascular density represents the ratio of the total surface area of the retinal layer to its surface occupied by vessels, which is established with the help of optical coherence tomography in non-contrast angio mode, namely if the vascular density is 25.5 and lower.

[0008] The method of treatment of severe non-proliferative diabetic retinopathy using laser therapy is known in order to prevent the onset of the process of hypoxia in the retinal layers, which subsequently leads to retinal neovascularization (development of proliferative diabetic retinopathy). According to the SRD protocol (Study of Diabetic Retinopathy), the values of the laser spot to obtain gray-white burns are as follows: spot diameter 100…500 micrometers and current strength 200…700 mW and duration of action 100…200 ms [1].

[0009] The disadvantages of the known method are that conventional retinal photocoagulation with the mentioned laser values has significant side effects, such as, patient discomfort during treatment, large and permanent retinal scars, long duration of treatment (sometimes in several sessions), possible choroidal detachments after treatment, increased intraocular pressure with severe forms of glaucoma, decreased peripheral vision/chromatic vision/night vision.

[0010] The problem solved by the invention consists in proposing an effective treatment method for the severe form of non-proliferative diabetic retinopathy with the establishment of effective and non-traumatic values of the laser spot, which eliminates the disadvantages of the known method, which leads to the prophylaxis of the occurrence of the severe form of glaucoma, leads to the prophylaxis of the appearance of scars on the retina after the action of the laser, which would require additional invasive and expensive interventions for their removal, which would lead to the prophylaxis of choroid detachment and decreased peripheral vision/chromatic vision/night vision.

[0011] The essence of the invention consists in performing argon laser therapy in the green range, with a wavelength of 532 nm, with the spot values: spot diameter of 50…100 µm, current power of 100…180 mW and duration of action of 0.05…0.09 sec, simultaneously administering alpha-lipoic acid 600 mg, 1 tablet per day, for 3 months, pentoxifylline retard 400 mg, 1 tablet 2…3 times per day, for 3 months, a mixture containing thiamine hydrochloride 250 mg, pyridoxine hydrochloride 250 mg and cyanocobalamin 1 mg, one tablet per day, for 2 months.

[0012] The result of the invention consists in performing an effective treatment of the severe form of non-proliferative diabetic retinopathy due to the establishment of effective and non-traumatic values of the laser when its beam acts on the retina, an effective long-term treatment without the need for additional invasive and expensive interventions to eliminate complications, reduces the duration of treatment because it has a non-aggressive action on the retinal tissue, which reduces the duration of hospitalization by two times.

[0013] The advantages of the proposed method are:

[0014] - the values of the argon laser in the green range, with a wavelength of 532 nm, are non-aggressive;

[0015] - leads to the prophylaxis of the occurrence of the severe form of glaucoma;

[0016] - does not lead to the appearance of scars on the retina after the laser action;

[0017] - does not require additional invasive and costly interventions to eliminate complications;

[0018] - reduces the duration of treatment, as it has a non-aggressive action on the retinal tissue;

[0019] - reduces the duration of hospitalization by half;

[0020] - leads to the prophylaxis of choroidal detachment;

[0021] - leads to the prophylaxis of peripheral vision/chromatic vision/night vision disorders.

[0022] The method is performed as follows. Argon laser therapy is performed in the green range, with a wavelength of 532 nm, with spot values: spot diameter of 50…100 µm, current power of 100…180 mW and duration of action of 0.05…0.09 sec, simultaneously administered alpha-lipoic acid 600 mg, 1 tablet per day, for 3 months; pentoxifylline retard 400 mg, 1 tablet 2…3 times per day, for 3 months; a mixture (benevron) containing thiamine hydrochloride (vitamin B1) 250 mg, pyridoxine hydrochloride (vitamin B6) 250 mg and cyanocobalamin (vitamin B12) 1 mg, one tablet per day, for 2 months.

[0023] Patients were treated according to the known method and according to the method of the described invention and the results were analyzed using optical coherence tomography in non-contrast angio mode and computerized perimetry according to the general program, demonstrating the effectiveness of the treatment according to the invention in patients with severe form of non-proliferative diabetic retinopathy (Table 1 and 2).

[0024] Clinical cases (patients to whom laser spot values were applied following the SRD protocol, according to the known method).

[0025] Table 1

Patient

Applied laser spot values

Vascular density data in superficial layers on pre-laser non-contrast angiography OCT

Pre-laser general computerized perimetry data

Vascular density data in superficial layers on OCT non-contrast angiography regimen post-laser at 3 months

Post-laser general computerized perimetry data at 3 months (visual field)

Patient X.

Duration 120 ms Diameter 300 µm Power 350 mW

Medial quadrant 35.2 (average) Lateral quadrant 34.7 (average)

Small absolute superior and temporal scotoma

°

Concentrically tapered by about 20o

Patient Y.

Duration 150 ms Diameter 350 µm Power 400 mW

Medial quadrant 39.2 (average) Lateral quadrant 31.6 (average)

Narrowed supero-temporal by about 10o

Medial quadrant 36.9 (average) Lateral quadrant 29.6 (average)

Concentrically tapered by about 25o

Patient A.

Duration 180 ms Diameter 400 µm Power 450 mW

Medial quadrant 33.8 (average) Lateral quadrant 23.8 (average)

Narrowed supero-temporal by about 15o

Medial quadrant 30.7 (average) Lateral quadrant 20.9 (average)

Concentrically tapered by about 25…30o

Patient B.

Duration 200 ms Diameter 450 µm Power 510 mW

Medial quadrant 35.6 (average) Lateral quadrant 27.7 (average)

Absolute and relative peripheral scotomas

Medial quadrant 31.5 (average) Lateral quadrant 23.6 (average)

Concentrically tapered by about 30o

Patient E.

Duration 120 ms Diameter 380 µm Power 410 mW

Medial quadrant 40.1 (average) Lateral quadrant 32.1 (average)

Absolute and relative peripheral and paracentral scotomas

Medial quadrant 37.8 (average) Lateral quadrant 29.5 (average)

Concentrically tapered by about 25o

[0027] Clinical cases (patients to whom laser spot values were applied for mild retinal whitening, as well as the above-indicated drug treatment concomitantly with laser therapy, according to the invention).

[0028] Table 2

Patient

Applied laser spot values

Vascular density data in superficial layers on pre-laser non-contrast angiography OCT

Pre-laser general computerized perimetry data

Vascular density data in superficial layers on OCT non-contrast angiography regimen post-laser at 3 months

Post-laser general computerized perimetry data at 3 months (visual field)

Patient T.

Duration 0.07 s Diameter 100 µm Power 120 mW

Medial quadrant 38.2 (average) Lateral quadrant 36.7 (average)

Relative paracentral and single absolute peripheral temporal scotomas

Medial quadrant 38.3 (average) Lateral quadrant 35.9 (average)

Concentrically narrowed by about 5o, relative paracentral scotomas

Patient Z.

Duration 0.08 s Diameter 140 µm Power 160 mW

Medial quadrant 37.2 (average) Lateral quadrant 34.6 (average)

Narrowed supero-temporally by about 5o

Medial quadrant 35.9 (average) Lateral quadrant 32.6 (average)

Narrowed predominantly temporo-inferiorly by about 10°

Patient N.

Duration 0.1 s Diameter 180 µm Power 180 mW

Medial quadrant 38.9 (average) Lateral quadrant 32.1 (average)

Narrowed infero-temporally by about 5o

Medial quadrant 36.1 (average) Lateral quadrant 31.9 (average)

Concentrically tapered by about 10…15o

Patient F.

Duration 0.06 s Diameter 150 µm Power 150 mW

Medial quadrant 38.1 (average) Lateral quadrant 37.8 (average)

Absolute and relative peripheral scotomas

Medial quadrant 36.9 (average) Lateral quadrant 36.5 (average)

Narrowed supero-temporally by about 10o, relative paracentral scotomas

Patient C.

Duration 0.1 s Diameter 200 µm Power 170 mW

Medial quadrant 39.1 (average) Lateral quadrant 37.9 (average)

Absolute paracentral scotomas

Medial quadrant 38.0 (average) Lateral quadrant 35.4 (average)

Concentrically narrowed by about 10o, absolute paracentral scotomas

[0030] Analyzing the above tables, we can conclude that in patients with severe non-proliferative diabetic retinopathy, to whom laser coagulation with laser spot values according to the SRD protocol was applied, according to table 1, according to the known method, an obvious decrease in vascular density in the superficial and deep layers is determined in optical coherence tomography in non-contrast angio mode, as well as the appearance of aggressive changes in the visual field (from absolute scotomas to concentric narrowing of the visual field up to 25…30o). These changes established in these patients are apparently irreversible, which leads to a decrease in the quality of life of patients, by narrowing the visual field, due to the formation of drastic retinal scars post laser.

[0031] Studying the data of Table 2, the positive practical applicability of the method proposed for the invention, namely the values of the laser spot, as well as the above-indicated drug treatment concomitantly with laser therapy, is reflected. Thus, reversible post-laser scars appear in these patients, with small diagnostic changes, namely an insignificant decrease in vascular density in the superficial and deep layers at optical coherence tomography in non-contrast angio mode and the appearance of relative/absolute peripheral scotomas in the visual field (in some patients, narrowing of the visual field up to 10…15o), with the possibility of early rehabilitation of visual functions and visual field.

1. Everett LA, Paulus YM. Laser Therapy in the Treatment of Diabetic Retinopathy and Diabetic Macular Edema. Curr. devil Rep. 2021 Sep 6, vol 21(9), p 35. doi: 10.1007/s11892-021-01403-6. PMID: 34487257; PMCID: PMC8420141

Claims (1)

1. Method of treatment of the severe form of non-proliferative diabetic retinopathy, which consists in performing argon laser therapy in the green range, with a wavelength of 532 nm, with spot values: spot diameter of 50…100 µm, current power of 100…180 mW and duration of action of 0.05…0.09 sec, simultaneously administering alpha-lipoic acid 600 mg, 1 tablet per day, for 3 months, pentoxifylline retard 400 mg, 1 tablet 2…3 times a day, for 3 months, a mixture containing thiamine hydrochloride 250 mg, pyridoxine hydrochloride 250 mg and cyanocobalamin 1 mg, one tablet per day, for 2 months.