Glaucoma Remission

:Remission & Glaucoma

A nerve cell may alive but not fully functional. Such a cell may be able to be brought back to a level of effective visual function, whether it be by improved circulation, enhanced cellular metabolism, etc. If such physiological cellular changes occur in a large enough population of cells, this improvement can show up on your visual field test.

This can occur with significant reduction of IOP, with some cases improving progressively over a year or more. Improvements are more frequent in younger patients and in open angle glaucoma (versus low tension glaucoma).

The most common improvement is an alteration of differential light sensitivity across the visual field in patients with initial high ocular pressure, often above 30 mmHg, after successful reduction of pressure. The change in light sensitivity results in an improvement of the mean defect index, which can return back to normal, without change in the localized defect index. Foveal thresold is also improved by a similar magnitude.

Such change is probably the consequence of a relief from previous excessive pressure which directly alters the metabolism of the ganglion cells. It is possible that photoreceptor and choroidal metabolism are involved in the pathogenesis of visual defects seen in excessively hypertensive glaucomas and that improvement occurs at these levels as well.

Scotomas can reduce in size and in depth.

This process is slower than diffuse improvement and appears in patients well controlled over many months. This phenomenon is less understandable than differential light sensitivity changes. It may be due to better function of the remaining ganglion cells, with an increase in their receptive field area. Indeed, it is known that ganglion cell receptive fields in the retina are not definitely fixed in size but are modulated chemically by neurotransmitters.

Occasionally, even absolute scotomas can improve and transform into relative defects but such cases are exceptional and are related to a dramatic reduction of highly excessive intraocular pressure.

Many studies using psychophysical testing methods like spatial or temporal contrast sensitivity have shown that visual function can improve in glaucoma. With classical kinetic Goldmann perimetry, up to 40% of ganglion cells must be non-functioning to detect a diffuse defect. Goldmann perimetry is not sensitive enough to detect subtle changes. Static automated perimetry can show an abnormality when 10% to 15% of the ganglion cells suffer. Many signs of glaucoma can show positive change: intraocular pressure can be reduced, normal ocular blood flow can be restored, and optic nerve head cupping can decrease, especially after surgical treatment in juvenile glaucoma.

Jean-Philippe Nordmann in Paris, France.

Disc & Field Improvements with Lower IOP:

Eyes with early to moderate COAG can show reversal of optic disc cupping and visual field improvement following a large magnitude of IOP reduction.

Tsai CS, Shin DH, Wan JY, Zeiter JH (1991) Visual field global indices in patients with reversal of glaucomatous cupping following IOP reduction. Ophthalmology 98:1412-1419).

Improvement of visual function, as well as reversal of disc cupping, is possible if the IOP is normalized prior to atrophy of the nerve fibers.

Greve EL, Dake CL, Verduin WM (1977) Pre- and postoperative results of static perimetry in patients with glaucoma simplex. Doc Ophthalmol 42: 335-351

Iwata K (1979) Reversible cupping and reversible field defect in glaucoma. Doc Ophthalmol Proc 19:233-239; Shin DH (198 1) Trabeculectomy. Int Ophthalmol Clin 21:47-68).

One third of patients with glaucoma have a photographically visible improvement in the optic disc following lowering of intraocular pressure of at least 30%.

Katz LJ, Spaeth GL, Cantor LB, et al. Reversible optic disc cupping and visual field improvement in adults with glaucoma. Am J Ophthalmol 1989;107(5): 485-492.

An improvement in the appearance of the optic disc or visual field may be a way to establish a satisfactory level of intraocular pressure in individual glaucoma patients.

Spaeth GL: A new management system for glaucoma based on improvement of the appearance of the optic disc or visual field. Fortschritte Der Ophthalmologie 1988;85(6):614-619

Spaeth GL: Reversibility of optic disc cupping. A phenomenon that may change the management of glaucoma (editorial; comment). Arch Ophthalmol 1989;107(11):1583-1584

Spaeth GL, Katz LJ, Poryzees E et al: Is improvement of the optic disc or visual field in patients with glaucoma a sign of clinical importance? Invest Ophthalmol & Vis Sci 1989;30:421

Spaeth GL, Fellman RL, Starita RL et al: A new management system for glaucoma based on improvement of the appearance of the optic disc or visual field. Trans Am Acad Ophthalmol Otolaryngol 1985;83:269-284.

Vitamin B12 & Fields

One 5 year study shows that 1500 mcg/day of vitamin B12 stops the progression of visual field loss in glaucoma, and a significant percentage of patients actually have some vision restored. Vitamin B12 deficiency can cause optic nerve atrophy.

Alpha Lipoic Acid & Visual Function

Improvement in visual function is seen in 45% of glaucoma patients supplemented with alpha lipoic acid in a controlled trial.

Filina AA, Davydova NG, Endrikhovskii SN, Shamshinova AM. Lipoic acid as a means of metabolic therapy of open-angle glaucoma. Vestn Oftalmol 1995;111:6-8. (Article in Russian)

Supplementation of alpha lipoic acid can increase glutathione in red blood cells of patients with glaucoma.

Bunin AI, Filina AA, Erichev VP. A glutathione deficiency in open-angle glaucoma and the approaches to its correction. Vestn Oftalmol 1992;108:13-15. (Article in Russian)

Supplementation of alpha lipoic acid can also increase glutathione in lacrimal fluid of patients with glaucoma.

Filina AA, Davydova NG, Kolomoitseva EM. The effect of lipoic acid on the components of the glutathione system in the lacrimal fluid of patients with open-angle glaucoma. Vestn Oftalmol 1993;109:5-7. (Article in Russian))

Both Alpha Lipoic Acid and N-Acetyl Cysteine are effective ways of increasing glutathione levels.

Ginkgo biloba & Severe Field Loss

Forty-six patients with severe visual field disturbances or serious retinal vascular degeneration were given 160 mg/day Ginkgo biloba extract for four weeks, then 120 mg/day. Progress was assessed monthly by measuring visual acuity, visual fields, fundus exam, IOP, blood pressure, and pulse rate. Improvements were observed.

Merte HJ, Merkle W. Long-term treatment with Ginkgo biloba extract of circulatory disturbances of the retina and optic nerve. Klin Monatsbl Augenheilkd 1980;177:577-583.

Ginkgo biloba increases blood flow to the ophthalmic artery even in healthy subjects.

Chung HS, Harris A, Kristinsson JK, et al. Ginkgo biloba extract increases ocular blood flow velocity. J Ocul Pharmacol Ther 1999;15:233-240.

In a prospective, randomized, placebo-controlled, double-masked crossover trial at the Glaucoma Center, Clinica Oculistica Università di Brescia, and the Clinica Oculistica, Università di Catania, in Italy, GBE improves preexisting visual field damage in some patients with normal tension glaucoma (NTG). 27 patients with bilateral visual field damage resulting from NTG received 40 mg GBE orally three times daily for four weeks, followed by a washout period of eight weeks, and then four weeks of placebo treatment (40 mg fructose). Other patients took the fructose first and the GBE last. Visual field tests were performed at baseline and the end of each phase of the study. Significant improvement in visual fields indices were found after GBE treatment. Mean deviation (MD) at baseline was 11.40 +/- 3.27 dB versus 8.78 +/- 2.56 dB MD after GBE treatment; corrected pattern standard deviation (CPSD) at baseline was 10.93 +/- 2.12 dB versus 8.13 +/- 2.12 dB CPSD after GBE treatment. No significant changes were found in intraocular pressure (IOP), blood pressure, or heart rate after placebo or GBE treatment. The study concluded that ginkgo biloba extract administration improves preexisting visual field damage in some patients with NTG.

Quaranta L, Bettelli S, Uva MG, Semeraro F, Turano R, Gandolfo E. Effect of Ginkgo biloba extract on preexisting visual field damage in normal tension glaucoma. Ophthalmology 2003;110: 359-62.

Magnesium, Circulation & Fields

In a study of ten patients, six with open-angle glaucoma and four with normal-tension glaucoma, all suffering from cold-induced vasospasms of the extremities and all with marked visual field deficits, despite normal or drug-normalized IOP, 243 mg/day of Magnesium improved both circulation and visual fields in 8 patients (80%) in 4 weeks.

Gaspar AZ, Gasser P, Flammer J. The influence of magnesium on visual field and peripheral vasospasm in glaucoma. Ophthalmol 1995;209:11-13.

Magnesium is nature's Calcium channel blocker. The average American diet is deficient in Magnesium. The best absorbed form is Magnesium Glycinate.

Calcium Channel Blocking Drugs & Fields

In patients with digital vasospasm documented by a local capillary cooling test, visual fields worsened after placing one hand in cold water and improved after treatment with systemic nifedipine, a calcium channel blocker.

Gasser P, Flarnmer J. Influence of vasospasm on visual function. Doc Ophthalmol 1987;66:3-18; Gasser P, Flammer J, Guthauser U, Mahler F. Do vasospasms provoke ocular diseases? Angiology 1990;41:213-20.

Kitazawa and coworkers treated 25 patients with low-tension glaucoma with systemic nifedipine for a period of 6 months. Although this study had no control group for comparison, six patients showed sustained improvement in visual fields during the course of the study.

Kitazawa Y, Shirai H, Go FJ. The effect of Ca2+-antagonist on visual field in low-tension glaucoma. Graefes Arch Clin Exp Ophthalmol 1989;227:408-12

Similarly, contrast sensitivity was significantly improved 2 h after a single dose of oral nimodipine in 14 patients with low-tension glaucoma and 17 control subjects.

Bose S, Piltz JR, Breton ME. Nimodipine, a centrally active calcium antagonist, exerts a beneficial effect on contrast sensitivity in patients with normal-tension glaucoma and in control subjects. Ophthalmology 1995;102:1236-41

See an example of visual field improvement in low-tension glaucoma following treatment with a systemic calcium channel blocker.

The short-term influence of nifedipine was evaluated in 59 patients with visual field defects: 38 with optic nerve head pathology and 21 with normal-appearing optic nerves. A statistically significant improvement of the visual fields was observed following treatment with systemic nifedipine. This effect was more pronounced in younger patients and those with normal-appearing optic nerve heads. In patients with visual field improvement, the changes were observed in scotomatous and nonscotomatous areas.

Caspar AZ, Flammer J, Hendrickson P. Influence of nifedipine on the visual fields of patients with optic-nerve-head diseases. Ear J Ophthalmol 1994;4:24-8

The effect of the calcium channel blocker brovincamine fumarate on visual field changes in low-tension glaucoma was studied in a prospective, placebo-controlled study. Brovincamine dilates intracranial vessels more selectively than does nifedipine, minimizing adverse side effects of peripheral vasodilation, including facial flushing and orthostatic hypotension. After a minimum follow-up of 2.5 years, Humphrey Statpac 2 linear regression analysis indicated that 6 (43%) of 14 treated eyes had improved visual fields, with no significant change in the other 8 patients. In contrast, none of the control patients had visual field improvement, 2 had visual field deterioration, and 12 had unchanged visual fields. Analysis of the visual field outcomes showed a statistically significant difference of the treated group compared with controls, indicating an association between improved visual field prognosis and use of this calcium channel blocker.

Sawada A, Kitazawa Y, Yamamoto T, Okabe I, Ichien K. Prevention of visual field defect progression with brovincamine in eyes with normal-tension glaucoma. Ophthalmology 1996; 103:283-8.

Carbonic Anhydrase Inhibitors, Circulation & Fields

A controlled, unmasked clinical trial of topical dorzolamide as monotherapy followed 31 patients with a confirmed diagnosis of primary open-angle glaucoma in both eyes for a mean of nine months. Patients applied dorzolamide eye drops in both eyes three times daily. In a randomly chosen eye, IOP, optic nerve head blood flow, ocular pulse amplitudes, pulsatile ocular blood flow, and visual fields were measured. IOP dropped after nine months of therapy from 18 to 15 mm Hg (P<0.01). Humphrey 30-2 visual fields improved from MD -11.71 to -8.06 dB (P<0.05). Optic nerve head blood flow increased from 508 AU at baseline to 644 AU. Pulsatile ocular blood flow improved from 542 to 676 µl/min (P<0.05). Investigators found no significant correlation between visual field changes and pulsatile ocular blood flow.

Carbogen, Circulation & Fields

Provoked vasodilation (calcium channel blockers, carbon dioxide) improves ocular hemodynamics in normal pressure glaucoma patients. The Carbogen-test (95 % O2 and 5 % CO2 in a partly closed rebreathing system) provoked vasodilation during visual field testing (Humphrey 30-2). Visual fields were performed in room air versus carbogen. Patients with primary high pressure glaucoma (n = 204, age = 66 years, 110 female, 94 male) and normal pressure glaucoma (n = 23, age 62 years, 14 female, 9 male) were tested for a visual field change exceeding the short time fluctuation. The visual field of 49 patients (24 %) suffering from primary open angle glaucoma improved significantly (p < 0.001) during carbogen breathing (MD-Baseline x =-13.52; MD-visual field (MD-Baseline: x = -13.21; MD-Carbogen: x = -13.68). The normal pressure glaucoma group showed visual field improvement in 8 patients (35 %) with the MD improving from -13.49 to -3.79 dB (p < 0.01). The other normal pressure glaucoma patients did not show any significant changes of their visual field (MD-Baseline: x = -13.58; MD-Carbogen: x = -13.19 dB). Thus 35% of normal pressure glaucoma patients and 24% of high pressure glaucoma patients suffer from ocular vasospasm which is released by carbogen breathing.

A. G. Böhm, A. U. Koeller, L. E. Pillunat. Effect of Carbon Dioxide on Visual Function in Normal Pressure and High Pressure Glaucoma, University Eye Hospital Hamburg, Martinistr. 52, D-20246 Hamburg.

Salvia miltiorrhiza & Fields

Salvia miltiorrhiza (Dan Shen) is an herb used traditionally in oriental medicine. A study of 121 patients with middle to late stage glaucoma received a preparation made from the root of this herb for one month. Visual acuity improved in 43.8% of the eyes studied, while 49.7% showed increased visual fields (p<0.01 compared to untreated controls). Followups as long as 30 months continued to show either stable or improved visual fields.

Wu ZZ, Jiang YQ, Yi SM, Xia MT. Radix salviae miltiorrhizae in middle and late stage glaucoma. Chin Med J 1983;96:445-447.

Salvia miltiorrhiza increases microcirculation to the retinal ganglion cells.

Vaccinium myrtillus & Retinal Function

Eight glaucoma patients given a single dose of 200 mg anthocyanosides from Vaccinium myrtillus (bilberry) (e.g. 800 mg standardized at 25% anthocyanosides) showed measurable improvement in retinal function on electroretinography.

Caselli L. Clinical and electroretinographic study on activity of anthocyanosides. Arch Med Interna 1985;37:29-35.

These anthocyanosides also stabilize collagen, provide anti-oxidant protection and decrease capillary fragility.

Allergen-Avoidance & Fields

A study of 113 patients with chronic simple glaucoma showed immediate IOP increases of up to 20 mm Hg upon challenge (exposure) with food or other allergens. Another study of 3 individual cases of simple glaucoma, showed that elimination of food allergens markedly improved treatment outcomes compared to treatment with drugs and surgery or drugs alone. In one case, intraocular pressure could only be controlled once allergens were eliminated from the diet. In two other cases, despite adequate control of IOP with a combination of drugs and surgery, visual field loss continued to progress. Visual fields actually improved markedly upon beginning an allergen-free diet. Sjogren was the first to identify the relationship between allergy and IOP.

Light & Fields

Syntonic phototherapy using color stimulation of the retina has been shown to increase visual fields in a number of studies in various populations, not including glaucoma. We do know that full spectrum light reduces hip fractures by 50%, while medical treatment for glaucoma has been shown to increase hip fractures by over 300%. This is especially important not just because medical treatment for hip fracture costs $25,000 per patient, but because one third of these patients die within one year following the trauma.

Clothing & Fields

Neckties can increase IOP by compressing the jugular veins, reducing veinous drainage from the head and eye area. In one study, 67% of businessmen in normal health wore neckties tight enough to reduce visual performance.

Circulation Improvement:

Demonstrable improvement in blood flow following lowering intraocular pressure may be a method of establishing what level of intraocular pressure is adequate in each individual with glaucoma.

Spaeth GL, Vacharat N: Provocative tests and chronic simple glaucoma. I. Effect of atropine on the water drinking test: Intimations of central regulatory control. II. Fluorescein angiography provocative test. A new approach to separation of the normal from the pathological. Br J Ophthalmol 1972;56(3):205-216.

Blood flow to the optic nerve improves after successful trabeculectomy.

Trible JR, Costa VP, Sergott RC, Spaeth GL et al: The influence of primary open-angle glaucoma upon the retrobulbar circulation: baseline, postoperative and reproducibility analysis. Trans Am Ophthalmol Soc 1993;91:245-265.

Glaucoma Preventive Agents & Functions:

Melatonin (Sleep) vs Cortisol (Stress) & Diurnal IOP

IOP varies throughout the day, typically with the lowest pressure in the very early morning hours. IOP parallels fluctuations in cortisol, a stress-related adrenal hormone, with high cortisol conferring higher IOP. Diurnal variations in IOP are more pronounced in people with glaucoma (>10 mmHg) compared to 3-7 mmHg variations in non-glaucomatous eyes. Melatonin levels peak around 2 a.m. when IOP is on a downward trend.

Samples JR, Krause G, Lewy AJ. Effect of melatonin on intraocular pressure. Curr Eye Res 1988;7:649-653.

With normal IOPs and no glaucoma, IOPs are maximum at 4-6 p.m. and minimum at 2-5 a.m. Exposure to bright light, which suppresses melatonin secretion, reduces the early-morning fall in IOP. 200 mcg melatonin given to the bright-light group resulted in a significant drop in IOP starting within an hour and lasting up to four hours. Beta-blockers used in medical treatment of glaucoma decrease melatonin levels, which explains why topical timolol does not work as well in the evening.

Topper J, Brubaker R. Effects of timolol, epinephrine and acetazolamide on aqueous flow during sleep. Invest Ophthalmol Vis Sci 1985;26:1315-1319.

CoQ10 & Prevention of Cardiac Side Effects of Timolol

The beta-blocker timolol can have significant cardiac side effects, including bradycardia and heart failure.

Beers MH, Berkow R, eds. Merck Manual, Centennial Edition. Whitehouse Station, NJ: Merck Research Laboratories; 1999.

Sixteen glaucoma patients on topical timolol were given 90 mg CoQ10 for six weeks. CoQ10 delayed the appearance of negative inotropic effects, including bradycardia, associated with timolol, preventing the negative cardiac effects of the drug without interfering with its effect on IOP.

Takahashi N, Iwasaki T, Sugiura T, et al. Effect of coenzyme Q10 on hemodynamic response to ocular timolol. J Cardiovasc Pharmacol 1989;14:462-468.

Forskolin & IOP-Reduction via Inflow

The triterpene forskolin in Coleus forskohlii stimulates the enzyme adenylate cyclase.

Caprioli J, Sears M, Bausher L, et al. Forskolin lowers intraocular pressure by reducing aqueous inflow. Invest Ophthalmol Vis Sci 1984;25:268-277.

Adenylate cyclase stimulates the ciliary epithelium to produce cyclic adenosine monophosphate (cAMP), which decreases IOP by decreasing aqueous humor inflow.

Caprioli J, Sears M. The adenylate cyclase receptor complex and aqueous humor formation. Yale J Biol Med 1984;57:283-300.

Forskolin can significantly decrease IOP compared to placebo.

Meyer BH, Stulting AA, Muller FO, et al. The effect of forskolin eye drops on intra-ocular pressure. S Afr Med J 1987;71:570-571.

In eight healthy subjects one drop of forskolin significantly decreased IOP and flow rate was diminished an average of 34 percent.

Burstein NL, Sears ML, Mead A. Aqueous flow in human eyes by forskolin, a potent adenylate cyclase activator. Exp Eye Res 1984;39:745-749.

Oral standardized extracts of Coleus forskohlii are known to raise cAMP as its mechanism of action in various disease conditions.

Rule Out or Replete Vitamin/Mineral Deficiencies Associated with Glaucoma, IOP Elevation and Ganglion Cell Degeneration:

Thiamin Malabsorption & Ganglion Cell Degeneration

Thiamin (vitamin B1) is deficient in some glaucoma patients. Blood levels and dietary intakes of B1 were examined in 38 glaucoma patients and 12 controls. The glaucoma patients demonstrated a significantly lower blood levels of thiamin, which was not due to diet indicating impaired absorption.

Asregadoo ER. Blood levels of thiamine and ascorbic acid in chronic open-angle glaucoma. Ann Ophthalmol 1979;11:1095-1100.

Thiamin deficiency is associated with degeneration of ganglionic cells in the brain and spinal cord, and may affect degeneration of the optic nerve.

Chromium Deficiency & IOP

Chromium deficiency causes elevation of IOP in humans and primary open-angle glaucoma patients have decreased erythrocyte chromium levels.

Lane BC. Evaluation of intraocular pressure with daily, sustained closework stimulus to accommodation, lowered tissue chromium and dietary deficiency of ascorbic acid. Doc Ophthalmol 1980;28:149-155.

Vitamin C & Outflow Facility

Some studies show Vitamin C deficiency in glaucoma patients. Vitamin C, an osmotic agent which the ciliary body actively concentrates into the aqueous humor, stimulates synthesis of hyaluronic acid in trabecular meshwork from glaucomatous eyes in vitro.

Schachtschabel DO, Binninber E. Stimulatory effects of ascorbic acid in hyaluronic acid synthesis of in vitro cultured normal and glaucomatous trabecular meshwork cells of the human eye. Z Gerontol 1993;26:243-246.

Ascorbate reduces the viscosity of hyaluronic acid and increases outflow through the trabecular meshwork.

Liu KM, Swann D, Lee P, Lam KW. Inhibition of oxidative degradation of hyaluronic acid by uric acid. Curr Eye Res 1984;3:1049-1053.

Categories of Glaucoma Remedies:

Fluid Metabolism: carbonic anhydrase inhibitors, Osmotic agents (e.g. high dose Vitamin C), Microwater (10X better tissue and lymph penetration for nutriture and detoxification)

Extracellular Communication: ANS/Endocrine: cholinergic agonists, cholinesterase inhibitors, adrenergic agonists, b-blockers, stress reduction

Cell Membrane Communication: Calcium Channel Blockers: Magnesium, Calcium Channel Blocking drugs.

Intracellular Communication: prostaglandins (homeopathic), prostaglandin precursors: Omega 3 EFAs, prostaglandin analogs, cAMP modulator (Forskolin), hormone: Melatonin (the only direct intracellular-acting hormone), growth-factors: NGF and synergists: ALC slows the age-related decline in the number of Nerve Growth Factor (NGF) receptors.

Antioxidant: Melatonin, Alpha Lipoic Acid, L-Carnosine, Ginkgo biloba, Vaccinium myrtillus

Neuroprotection against Excitotoxicity (Glutamate): L-Carnosine shows neuroprotection independent of its antioxidant activity.