• Professor of Ophthalmology for the Bascom Palmer Eye Institute at the University of Miami School of Medicine, 1990 to present
• Principal Investigator for The Extracellular Matrix in Glaucoma (1 RO1 EY 06662, 1986 to 1989), Principal Investigator for Core Grant for Vision Research (5 P30 EY02180-07, 1987 to 1992), and Co-Investigator for
5-Fluorouracil in Glaucoma Surgery (EY 05473, 1985 to 1990) for the National Eye Institute
• Founding member of the AGS
• President of the Pan-American Glaucoma Society, 1995 to 1997
• Recipient of the AAO's Senior Honor Award and of the International Glaucoma Review Award, 1998 and 2001, respectively
1. What was the impact of your early training at Washington University in St. Louis on your subsequent career?
The 9 wonderful years that I spent there consisted of a residency in ophthalmology, research and clinical fellowships in glaucoma, the chief residency, and 3 years on the faculty. Bernard Becker, MD, and Michael Kass, MD, were my fellowship mentors. Both had laboratory as well as clinical research interests, and they encouraged me to seek the same synthesis in my career. As Chairman, Dr. Becker provided me with a tissue culture laboratory where I could pursue my interests in trabecular cell culture and in steroids and glaucoma.
Dr. Becker had a phenomenal grasp of the scientific literature, including basic science and other fields of medicine. He was always looking for new concepts we could apply in ophthalmology and ways that we could collaborate with those in other fields. I followed that pattern. My experience in biochemistry and cell culture allowed me to introduce the nonvolatile, nontoxic buffer HEPES1 in corneal transplantation media for better pH stability and a color indicator to confirm the pH and the lack of infection. My collaboration with the Medicine Department on the natural history of diabetic retinopathy in insulin-dependent diabetes mellitus2 became the basis for the design of the Diabetes Control and Complications Trial (DCCT). The tissue culture laboratory grant that I transferred to Bascom Palmer Eye Institute in Miami in 1980 played a role in the study of 5-fluorouracil (5-FU) by Mark Blumenkranz, MD, and Anthony Hajek, PhD.3
2. Has your doctoral training in biochemistry impacted your approach to glaucoma?
As a biochemist, I found it natural to approach problems such as diabetic retinopathy or glaucomatous damage as dose-response curves. When I was a member of the monitoring committee of the DCCT, my question was, “What is the relationship between the level of glycosylated hemoglobin (HgbA1c) and the risk of progressive retinopathy?” With the Advanced Glaucoma Intervention Study (AGIS) and Comparison of Initial Glaucoma Treatments Study (CIGTS), my question was, “What is the relationship between IOP and the risk of glaucomatous progression in patients at different stages of the disease?”
In the DCCT, the biostaticians initially resisted my suggestion to look at the progression of retinopathy versus the level of HgbA1c, but they later reported about a 50% reduction in risk for each percentage of lower HgbA1c.4,5 The AGIS generated a clear dose-response curve that favored a low range of normal IOP in advanced cases.6 In the CIGTS, the 35% or greater lowering of IOP called for by the protocol was so successful that no net progression occurred, so no dose-response information was generated. Unlike in the AGIS, minimally damaged eyes in the CIGTS tolerated pressures in the upper teens so long as a 35% IOP reduction was achieved.7 The studies supported the 1959 observation of Paul Chandler, MD, that the relationship between IOP and the risk of progression depends upon the stage of the disease, with more damaged eyes requiring lower pressures than the population-average IOP for optimal results.8
3. What major paradigm changes occurred in your surgical management of open-angle glaucoma?
Based upon the laboratory and animal studies of Dr. Blumenkranz9 and Richard Parrish II, MD,10 I began using 5-FU in complex filtering surgery in May 1982. After my colleagues and I gained experience in complex cases,11 I began using 5-FU in primary filtering surgery in 1988 and mitomycin C in 1991.
The whole strategy of filtering surgery changed with the introduction of antifibrotics. The goal became to set an ideal target pressure of 8 to 12 mm Hg (near episcleral venous pressure) through a combination of a valve-like incision (to avoid hypotony later), titrated flap-suture tension, and antifibrotics to prevent the formation of additional resistance. Glaucoma surgery became far more predictable and successful.
Two subsequent developments have greatly reduced the incidence and/or consequence of the complications associated with antimetabolite surgery. The first was our method for repairing hypotony maculopathy.12 The second was the idea of Peng Khaw, MD, PhD, to apply mitomycin C widely with thin sponges under a fornix-based conjunctival flap to avoid leaks and infection.13
4. What reasoning directed you to the idea of conjunctival (external) compression sutures?
The idea occurred to me while examining a one-eyed patient with a traumatic leak at the lateral edge of a thin bleb. I thought that I could wall off the leak with a radial compressing stitch. The technique worked. Later, James Robinson, MD, then a Fellow, suggested the current mattress stitch configuration in which the surgeon anchors a 9–0 nylon suture in front with a short horizontal bite in the cornea, passes it over the bleb, anchors the suture behind the bleb with a horizontal bite in thick Tenon's, then passes the suture forward again over the bleb, and ties it.14
The approach was useful for walling off leaks at the sides of a bleb but not, as I had hoped, for allowing central bleb leaks to heal. Later, it occurred to me that bleb compression sutures would be useful for permanently lowering the profile of a bleb that was causing a dellen or bubble dysesthesia.14
5. What have been your rewards from training foreign glaucoma fellows?
During a trip to Costa Rica in 1986, the country's Health Minister asked me if my department could offer fellowships to their ophthalmology residents. Due to Florida law, we could only have them as observers. The first, Luis Villalobos, MD, stayed with his wife at my home. My family has hosted approximately one-third of the 105 Observer Fellows and Research Fellows from 26 countries and five continents.
The Research Fellows have amply rewarded me by making important contributions to studies of the long-term outcomes of antifibrotic filtering surgery, in which we have demonstrated no net visual field progression in 10 years at a low range of normal pressures.15-17
Additionally, the majority of Observer Fellows now teach in residency programs, and some have founded Glaucoma Fellowships. In their countries, they have introduced proper gonioscopy and the use of antifibrotics in glaucoma surgery. I hope that I have also taught them how to obtain an informative history from patients, how to explain glaucoma and its treatment with analogies patients can understand, and how to instill hope and confidence in patients and students. My fellows know that they can best “repay” me for their training by aiding the patients and students who can least repay them (Matthew 25:40).
1. Waltmann SR, Palmberg PF. Human penetrating keratoplasty using modified M-K medium. Ophthalmic Surg. 1978;9:48-50.
2. Palmberg P, Smith M, Waltmann S, et al. The natural history of retinopathy in insulin-dependent juvenile-onset diabetes. Ophthalmology. 1981;88:613-618.
3. Blumenkranz MS, Claflin A, Hajek AS. Selection of therapeutic agents for intraocular proliferative disease. Cell culture evaluation. Arch Ophthalmol. 1984;102:598-604.
4. Diabetes Control and Complications Trial Research Group. The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the diabetes control and complications trial. Diabetes. 1995:44:968-983.
5. Diabetes Control and Complications Trial Research Group. Progression of retinopathy with intensive versus conventional treatment in the Diabetes Control and Complications Trial. Ophthalmology. 1995;102:647-661.
6. The AGIS Investigators. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. Am J Ophthalmol. 2000;130:429-440.
7. Lichter PR, Musch DC, Gillespie BW, et al, CIGTS Study Group. Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to medications or surgery. Ophthalmology. 2001;108:1943-1953.
8. Chandler PA. Long-term results in glaucoma therapy. Am J Ophthalmol. 1960;49:221-246.
9. Blumenkranz MS, Ophir A, Claflin AJ, Hajek A. Fluorouracil for the treatment of massive periretinal proliferation. Am J Ophthalmol. 1982;94:458-467.
10. Gressel MG, Parrish RK 2nd, Folberg R. 5-Fluorouracil and glaucoma filtering surgery: I. An animal model. Ophthalmology. 1984;91:378-383.
11. Rockwood EJ, Parrish RK 2nd, Heuer DK, et al. Glaucoma filtering surgery with 5-fluorouracil. Ophthalmology 1987;94:1071-1078.
12. Suner IJ, Greenfield DS, Miller MP, et al. Hypotony maculopathy after filtering surgery with mitomycin C. Incidence and treatment. Ophthalmology. 1997;104:207-214; discussion: 214-215.
13. Wells AP, Cordeiro MF, Bunce C, Khaw PT. Cystic bleb formation and related complications in limbus-versus fornix-based conjunctival flaps in pediatric and young adult trabeculectomy with mitomycin C. Ophthalmology. 2003;110:2192-2197.
14. Palmberg PF. Complications of glaucoma filtering surgery. In: Leader B, Calkwood JC, eds. Proceedings of the New Orleans Academy of Ophthalmology. Nerve Under Peril. Vol 45. Brussels, Belgium: B. Karger, Co.; 1998: 183-193.
15. Ishida K, Benz EE, Schiffman JC, Palmberg PF. Long-term results of primary filtering surgery with adjunctive antimetabolites. Paper presented at: The ARVO Annual Meeting; May 6, 2003; Fort Lauderdale, FL.
16. Palmberg P. Evidence-based target pressures: how to choose and achieve them. Int Ophthalmol Clin. 2004;44:1-14.
17. Palmberg P, Ishida K. One-site cataract and glaucoma surgery. In: Coleman AE, Morrison JC, eds. Combined Cataract and Glaucoma Surgery. Martin Dunitz: London and New York; 2005: 87-100.
