Research and Clinical Statuses of
Glaucoma at the Beginning of 2004
Summary

Basically, there is no indication that any more mileage in eyesight is being achieved today than there was in 1993, when my prior discussion was assembled here.  There has been considerable research done, however; and quite a bit of knowledge accumulated, at least in tentative form, on what some of the causes of and developments in glaucomatous degeneration of optic nerve heads actually are.  Unfortunately, such findings are still regarded as heretic to the Pressure Dogma that still supports most of the income of clinical glaucoma specialists and other ophthalmologists -- as viewed under consideration of the extensive loss of income and prestige that these practioners would experience, should they lose their beloved dogma prior to acquiring alternative therapies based mostly on achieving improved ocular blood flow by other than IOP lowering and/or by controlling apoptosis in optic nerves that show glaucomatous damage.  It's clear that many authors of both clinical and other research papers on this subject still fear to downplay the role of intraocular pressure in the loss of functionality in parts or all of people's visual fields, relative to direct effects of inadequate local blood flow to portions of optic nerves where they connect with the retinae, independent of any increases in IOP, lack thereof, or attempts to reduce IOP from any value short of at least 35 mmHg .

There have been numerous new topical medications approved for glaucoma and ocular hypertension, but all of these were designed only to lower IOPs.  They are described all over the Web and journal papers on their effectiveness and side effects may be found in Medline (U. S. National Medical Library).  A few of these, together with certain herbal remedies, have been claimed to affect ocular blood flow, but no such claim is well supported by peer-reviewed clinical journal articles.

I find very little additional attempt to correlate onsets of glaucoma with other ailments within the body of the same individual, past or current.  And I haven't seen anything new, during this update period, on any detailed genetic relationships to glaucoma.

Introduction

My reading of the medical journal articles on glaucoma, which formed the basis of my 1993 page on the subject, occurred during my own functionally observable glaucomatous loss of field only in the left eye -- from 1988 on until that eye stabilized in 1996 with only a trace of unusable peripheral vision.  I did not read much on the subject again until some time after last summer, when I started noting a significant scotoma in my right eye, only a degree or two from fixation.  When a reader of my glaucoma site, about a month ago, inquired as to the present situation in the glaucoma industry, I read the articles referenced at the end of this page, along with a few others, all of which form the basis of my discussion below.

The two opposing schools of glaucoma conceptualization, causal analysis and therapy are distinguished by an excellent, extensive broad-scope European and Brazilian survey paper from the blood-flow school, and a number of articles summerizing the results of several clinical trials based on pressure-reduction treatments of various glaucoma and ocular-hypertension cases as well as normal controls, from the IOP school.  In the survey paper, one can observe, particularly in its introduction, an incredible degree of deference shown toward the pressure aristocracy.  Indeed, organizations of the medical traditionalists hold sway over most of the money available for any kind of research on glaucoma, including that dispensed by governments.  On the other hand, the clinical-trial papers have to be read very carefully in order to unveil what is smeared over in their conclusions -- shrewed summaries set out to justify the traditionalists' pressure-reduction treatments until such time as these clinicians should be presented with delineated blood-flow-based treatment regimens.  Although considerable money and efforts have gone into oculovascular and "neuroprotection" research, on reading the results of it and considering the cloak held over it by the mystical depressurizers, one would have to judge that it will be more than two decades before there are any really effective non-pressure-lowering glaucoma treatments available at the general-public-accessible clinical level.  The term 'neuroprotection' was a great try as a political expedient in getting funding for research on means of stabilizing parts of the CNS, such as optic-nerve trunks; but have you ever heard of such terms as 'dermoprotection',  'ossiprotection', 'musculoprotection', etc.?  I doubt such buzz words will do much to solve the real problems in this political arena, let alone those in the lab and the clinic.

Alternatively, on the prosthetic scene, the problem of bypassing an optic nerve trunk electronically -- from an eyeglass-mounted camera to the visual center in the occipital lobe at the rear of the head (another link to an article on this project) -- is a much more ambitious project than bypassing a damaged retina, such as exists in a case of macular degeneration, with an electronic connection from such a camera to an intact optical nerve trunk.  Some implants of electronic chips that accomplish the latter connection are presently experimentally producing quite encouraging results in a sufferer or two of MD; but so far, experimental connections of the former type can only produce crude arrays of phosphene perceptions in glaucoma sufferers, to the accomplishment of possible awkward guidance through a well-lit doorway.

One might consider the delayed onset of glaucomatous loss of field in my second eye, after cessation of its progression in the first eye, as a matter requiring my conceding to the ophthalmological establishment on their claim that 'ya got it in one eye, ya got it in both,' and 'ya got it now, ya got it till ya die.'  However, I don't think the seven-year hiatus I experienced from cessation in progression in one eye until iniation of the problem in the other eye is at all common.  The eye-corralled ophthalms never cared to consider my suggestion that the serious nasal mucosal atrophy in my nose, on the same side as the first eye to go bad, was likely the cause of, or at least a causal factor in, the glaucoma in my first-attacked eye -- this in a person with no known extended-family history of glaucoma.  Of course now, my suggestion -- that possibly, but for an implant I had placed bilaterally in my nose a year and a half ago in attempt to alleviate the nasal problem, I might never have experienced any glaucoma in my fellow eye -- was completely rejected as making no sense.  I, of course, can't establish, to any decent degree of my own satisfaction, that such causal effects in either of my eyes actually describe a reality; but the reactions of MDs to such reasonable considerations emphasizes their almost universal holing up into their own little world -- in addition to their living 150 years back in history.  Of course, these particular possiblities of relationships, between cell atrophy in a neighboring organ and the same in one's eyes (glaucoma), could be relevant only to a quite small minority of cases of glaucoma.  However, the general principle of an initial defect common to more than one organ in an anatomical neighborhood, such as a local paucity of blood flow or other sort of regionally dispersed limitation, having consequences in all such organs, or having such consequences after transfer of the given defect from one organ to another therein, could turn out to be of wide applicablity to glaucoma treatment.  But I find no work reported on such patient-peculiar tie-ins, which I admit would be of less economic interest.

Non-Existent Body of this Discussion

Sorry, you'll have to read the individual papers listed below -- by either using a medical library open to the public, such as one at a state-run university or else by obtaining copies of them, for a price, via Medline or directly from the respective publisher, as either hard copy or in online form.  The links from the references below lead to abstracts of these papers in Medline.

I will point out this letter [Ref. 26] to a journal commenting on the claimed results of one of the glaucoma clinical trials.  It is additionally interesting that, as coming from an MD, it dumps the concern it mentions onto HMOs and pharmaceutical companies.  Be it made clear, though, it is the MDs and their powerful organizations that control what treatment modes are considered "standard medical procedures", and hence what drugs make money for these two entities.

I'll also reference this online article that rejects the entrenched NTG/NPG : OAG/POAG distinction within the glaucoma citadel.  This switch organizes glaucoma problems much more operationally, but it does not distinguish things causally.



References

1.  AGIS Investigators.  The Advanced Glaucoma Intervention Study: 1. Study design and methods and baseline characteristics of study patients.  Control Clin Trials. 1994 Aug;15(4):299-325.

2.  AGIS investigators.  Advanced Glaucoma Intervention Study 2.  Visual field test scoring and reliability.  Ophthalmology.  1994;113:396-400.
3.  Schulzer M.  Errors in the diagnosis of visual field progression in normal-tension glaucoma.  The Normal-Tension Glaucoma Study Group.  Ophthalmology 1994;101:1589-94; discussion 1595.

4.  [No authors listed]  Comparison of glaucomatous progression between untreated subjects with normal-tension glaucoma and subjects with therapeutically reduced introcular pressures.  Collaborative Normal-Tension Glaucoma Study Group.  Am J Ophthalmol 1998;126:487-97.  Erratum in: Am J Ophthalmol 1999 Jan;127(1):120.
5.  [No authors listed]  The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma.  Collaborative Normal-Tension Glaucoma Study Group.  Am J Ophthalmol 1998;126:498-505.

6.  Anderson DR.  Normal tension glaucoma study.  In:  Kertes PJ, Conway MD, eds.  Clinical Trials in Ophthalmology:  A Summary and Practice Guide.  Baltimore, Williams & Wilkins, 1998; chap 20.

7.  AGIS Investigators.  The Advanced Glaucoma Intervention Study: 3. Baseline characteristics of black and white patients.  Ophthalmology. 1998 Jul;105(7):1137-45.

8.   AGIS Investigators.  The Advanced Glaucoma Intervention Study: 4. Comparison of treatment outcomes within race. Seven-year results.  Ophthalmology. 1998 Jul;105(7):1146-64.

9.  Gordon MO, Kass MA.  The Ocular Hypertension Treatment Study.  Design and baseline description of the participants.  The Ocular Hypertension Treatment Study Group.  Arch Ophthalmol 1999;117:573-583.

10.  Schwartz AL, Van Veldhuisen PC, Gaasterland DE, Ederer F, Sullivan EK, Cyrlin MN. Related Articles, Links  The Advanced Glaucoma Intervention Study (AGIS): 5. Encapsulated bleb after initial trabeculectomy.  Am J Ophthalmol. 1999 Jan;127(1):8-19.

11.  AGIS Investigators.  The Advanced Glaucoma Intervention Study: 6. Effect of cataract on visual field and visual acuity.  Arch Ophthalmol. 2000 Dec;118(12):1639-52.

12.  AGIS Investigators.  The Advanced Glaucoma Intervention Study: 7. The relationship between control of intraocular pressure and visual field deterioration.  Am J Ophthalmol 2000;130:429-440.

13.  Anderson DR, Drance SM, Schulzer M; Collaborative Normal-Tension Glaucoma Study Group.  Natural history of normal-tension glaucoma.
Ophthalmology. 2001 Feb;108(2):247-53.

14.  Drance S, Anderson DR, Schulzer M; Collaborative Normal-Tension Glaucoma Study Group.  Risk factors for progression of visual field abnormalities in normal-tension glaucoma.  Am J Ophthalmol. 2001 Jun;131(6):699-708.

15.  AGIS Investigators.  The Advanced Glaucoma Intervention Study: 9. Comparison of glaucoma outcomes in black and white patients within treatment groups.  Am J Ophthalmol. 2001 Sep;132(3):311-20.

16.  AGIS Investigators.   The Advanced Glaucoma Intervention Study: 8. Risk of cataract formation after trabeculectomy.  Arch Ophthalmol. 2001 Dec;119(12):1771-9.
17.  Gaasterland DE, Blackwell B, Dally LG, Caprioli J, Katz LJ, Ederer F; Advanced Glaumoca Intervention Study Investigators. The Advanced Glaucoma Intervention Study (AGIS): 10. Variability among academic glaucoma subspecialists in assessing optic disc notching.  Trans Am Ophthalmol Soc. 2001;99:177-84; discussion 184-5.

18.  Flammer J, Orgul S, Costa VP, Orzalesi N, Krieglstein GK, Serra LM, Renard JP, Stefansson E.  The impact of ocular blood flow in glaucoma.
Prog Retin Eye Res. 2002 Jul;21(4):359-93. Review.

19.  Heijl A, Leske MC, Bengtsson B, Hyman L, Bengtsson B, Hussein M; Early Manifest Glaucoma Trial Group.Reduction of intraocular pressure and glaucoma progression:  Results from the Early Manifest Glaucoma Trial.  Arch Ophthalmol.  2002;120:1268:1268-1279.

20.  Gordon MO, Beiser JA, Brandt JD, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, Parrish RK 2nd, Wilson MR, Kass MA.  The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma.  Arch Ophthalmol. 2002 Jun;120(6):714-20; discussion 829-30.
21.  AGIS Investigators.  Related Articles:  The Advanced Glaucoma Intervention Study (AGIS): 11. Risk factors for failure of trabeculectomy and argon laser trabeculoplasty.
Am J Ophthalmol. 2002 Oct;134(4):481-98.

22.  AGIS Investigators.  The Advanced Glaucoma Intervention Study:  12. Baseline risk factors for sustained loss of visual field and visual acuity in patients with advanced glaucoma.  Am J Ophthalmol. 2002 Oct;134(4):499-512.

23.  Heijl, A, Leske MC, Bengtsson B, Hussein M.; Early Manifest Glaucoma Trial Group.  Measuring Visual Field progression in the Early Manifest Glaucoma Trial.  Acta Ophthalmol Scand. 2003 Jun;81(3):286-93.

24.  Beck AD; Advanced Glaucoma Intervention Study.  Review of recent publications of the Advanced Glaucoma Intervention Study.
Curr Opin Ophthalmol. 2003 Apr;14(2):83-5. Review.

25.  Gillespie BW, Musch, DC, Guire, EG, et al.  The Collaborative Initial Glaucoma Treatment Study: baseline visual field and test-retest variability.  Invest Ophthalmol Vis Sci.  June 2003, 44 (6):2613-2620.

26.  Weene, LE.  Ocular hypertension treatment study results could be misconstrued.  Arch Ophthalmol. 2003 Jul;121(7):1070; author reply 1070. No abstract available.

27.  Anderson DR, Drance SM, Schulzer M; Collaborative Normal-Tension Glaucoma Study Group.  Factors that predict the benefit of lowering intraocular pressure in normal tension glaucoma.
Am J Ophthalmol. 2003 Nov;136(5):820-9.

28.  Hafez AS, Bizzarro RL, Lesk MR.  Evaluation of optic nerve head and peripapillary retinal blood flow in glaucoma patients, ocular hypertensives, and normal subjects.  Am J Ophthalmol. 2003 Dec;136(6):1022-31.