Herbert E. Kaufman

Last updated
Herbert Edward Kaufman
Born (1931-09-28) September 28, 1931 (age 92)
Brooklyn, New York
Nationality American
Alma mater Princeton University
Harvard University
Known for Glaucoma, protease inhibitor, virology, Corneal transplant, Excimer laser, Photorefractive keratectomy, LASIK, Eye bank, Natamycin
AwardsWeisenfeld and Proctor awards from the Association for Research in Ophthalmology (ARVO)

MAP award from the Society Ophthalmoligica

Montgomery Medal from the Irish Ophthalmological Society

Contents

Pockington Medal from the Royal Society of Ophthalmology

Innovators award from the Association of Cataract and Refractive Surgeons
Scientific career
FieldsOphthalmology
Institutions NIH
University of Florida
Louisiana State University

Herbert Edward Kaufman (September 28, 1931) is an American ophthalmologist who discovered idoxuridine, the first clinically useful antiviral agent; co-developed with William Bourne the clinical specular microscope to view the live corneal endothelium, co-developed timolol with Thomas Zimmerman, a new class of medications to treat glaucoma; corneal storage media for eye banks; natamycin, the first commercially available medication to treat fungal infections of the eye; co-developed with Tony Gasset the use of bandage contact lenses; and was involved in the first laser vision photorefractive keratectomy of the eye with Marguarite McDonald. [1] [2]

Scientific career

He began his Princeton University education at age 16, where he graduated Phi Beta Kappa and Magna Cum Laude with a degree in chemistry. This was followed by medical school at Harvard University. Kaufman Graduated in 1956 Magna Cum Laude and Alpha Omega Alpha. He received the New England Pathology Society Award for developing a new type of calcium stain for histological tissue preparation. [1] [2]

He performed his Medical Internship at Massachusetts General Hospital, and following that, he worked at the National Institutes of Health (NIH) as a clinical associate for 2 years. While at the NIH much of his research concentrated on the parasite toxoplasma. He was the first to grow toxoplasma in culture. His studies showed that slow growing isolates of toxoplasma were more resistant to treatment and if fast growing toxoplasma isolates were slowed by reducing the temperature, they also became more resistant to treatment with pyrimethamine. [3]

Toward the end of his work at the NIH, Kaufman was asked to be the first Chairman of the Department of Ophthalmology at the University of Florida, in Gainesville, Florida. Since he had not yet begun his Ophthalmology residency, the University of Florida Medical School kept the position open until he completed his three-year residency at The Massachusetts Eye and Ear Infirmary of Harvard Medical School, under the training of Claus Dohlman. During his residency, he continued research in toxoplasmosis. He was assisted at this time and throughout his career by a chemical engineer, Emily Varnell. Kaufman became interested in finding a treatment for viral infections. Although there were vaccines to prevent some viruses, there was not a treatment for active viral infections. Kaufman believed that a medication could be found that would interfere with intracellular multiplication of a Herpes virus. During his residency, he pioneered the medical use of 5-iododeoxyuridine (IDU) the first medication to ever successfully treat and cure a viral infection. [2] [4]

Research and Discoveries

First Anti-Viral Medication: 5-iododeoxyuridine (IDU)

5-iododeoxyuridine (IDU) had been synthesized 8 years earlier by William Prusoff as an anticancer medication. Kaufman tested IDU as a possible agent to disrupt viral replication in active Herpes Simplex Virus infections of the eye. IDU was proven effective and resulted in the discovery of the first antiviral agent used in humans to treat an active viral infection. This agent was subsequently used to effectively treat Herpes Simplex keratitis, the primary cause of corneal blindness in the Western world at that time. [5] [6] Kaufman also developed the use of topical steroids in the treatment course of some corneal infections that were made worse by the host reaction to the infection. [Steroids and ISU Ref] The use of steroids reduced the damage produced by the host reaction and lessened the tissue damage that occurred as part of the infection. [7]

Glaucoma Medication: Timolol

Yale researcher Marvin Sears, observed that timolol, a beta-adrenergic agent, had an intraocular pressure lowering effect in rabbit eyes when used to dissolve lens zonules. There was reluctance among industry to investigate this drug further in trials because of the absence of a large market. Kaufman identified timolol as a possible therapeutic agent to treat glaucoma and with Thomas Zimmerman, conduct basic science and clinical trials with timolol, at the University of Florida. This introduced an entirely new class of drugs to treat glaucoma; it was ultimately marketed by Merck, Sharp and Dohme. [4] [8]

Fungal Corneal Infection Medication: Prymaricin (Natamycin)

While at the University of Florida, fungal infections of the eye were common and Kaufman sought to find an effective treatment for use on the eye. He read that a Dutch company used Prymaricin to prevent cheese from getting moldy. He designed an animal model of a fungal infection with which he and his colleague, Emanuel Newman, proved that the substance was efficacious for treating human infection. They provided Prymaricin to clinicians at no cost for a number of years. The medication ultimately received FDA approval without a clinical trial or a manufacturer. Alcon Laboratories later manufactured the drug as Natamycin. Prymaricin (natamycin) is still commonly used today. [4] [9]

Bandage Contact Lens

With Tony Gasset, Kaufman studied therapeutic soft contact lens (SCL) use to promote corneal healing and reduce pain. They also pioneered the use SCL and collagen shields as a sustained release mechanism for medication to the eye. [10]

Cornea Endothelium Microscopy (Specular Microscopy)

The specular microscope was developed with Bill Bourne, which showed that the human corneal endothelium divided little or not at all. Thus, this tissue must be protected since it could not effectively repair itself like other human tissue. This also led to the discovery that the corneal endothelium was being damaged during cataract surgery as the cataract was removed and the artificial lens was placed into the eye. [11]

Cornea Transplant Tissue storage

Prior to the development of corneal storage media for eye banks, corneal transplant surgery generally required corneal transplant surgery to be conducted with hours of the donor's death. This was not always possible; thus, the need for a corneal storage media was born out of need because of the dearth of usable cornea transplant tissue. [4] Kaufman proposed removing the corneas from the enucleated eyes and immersing the corneas in a type of tissue culture solution, which could maintain the health of the stored corneas for days. Kaufman immersed the corneal tissue in a tissue culture solution and later Dextran to dehydrate the tissue at the suggestion of colleague, Bernie McCarey, who validated the idea in 1974. [12]

There was resistance to this new procedure but with the support of Edward Maumenee, head of ophthalmology, Johns Hopkins University, Baltimore, the new protocol was accepted by Eye Banks International. MK media was not patented so that it could be used by eye banks throughout the world, free of charge. [4]

As eye banks required more time for tissue testing and distribution across the country, Kaufman developed K-Sol corneal storage media in 1986. K-sol contained chondroitin sulfate, which was a free radical scavenger to extend the usable life of the tissue in eye bank storage for up to 14 days. [13]

(k-sol reference) K-sol was used for many years but was removed due to a manufacturing contamination by Taylor Pharmacueticals. [14] Kaufman and Richard Lindstrom, modified the k-sol formulation to make Optisol corneal eye bank storage media in 1992. Optisol remains the most commonly used eye bank preserving medium, according to Kaufman. [15]

Laser Vision Correction

Ultimately, the first human to undergo laser vision correction with the excimer laser was a patient with a uveal melanoma in an eye slated for enucleation who allowed Marguerite McDonald to perform an excimer laser photorefractive keratectomy (PRK). Following enucleation, they performed histologic studies. This was followed by the same work in a series of blind patients who allowed PRK to be performed despite the absence of a benefit to them to forward this technology, which led to the development of LASIK eye surgery. [4] [16] Awards: The Weisenfeld and Proctor awards from the Association for Research in Ophthalmology (ARVO), the MAP award from the Society Ophthalmoligica, The Montgomery Medal from the Irish Ophthalmological Society, The Pockington Medal from the Royal Society of Ophthalmology, 10 outstanding Men of the year by the US Chamber of Commerce, The Innovators award from the Association of Cataract and Refractive Surgeons and others.

He was the editor of Investigative Ophthalmology and Visual Science and served on the Editorial Boards of a number of journals, including the AmericanJournal of Ophthalmology. He has been president of the Association for Research in Vision and Ophthalmology, the Contact Lens Association of Ophthalmologists, and the International Society of Refractive Keratoplasty and has served two terms on the Advisory Council of the National Eye Institute. He has more than 700 publications in his bibliography, including work on herpesvirus and ocular disease, antiviral drugs, corneal surgery, and refractive surgery. [2]

Related Research Articles

<span class="mw-page-title-main">Keratitis</span> Medical condition

Keratitis is a condition in which the eye's cornea, the clear dome on the front surface of the eye, becomes inflamed. The condition is often marked by moderate to intense pain and usually involves any of the following symptoms: pain, impaired eyesight, photophobia, red eye and a 'gritty' sensation.

<span class="mw-page-title-main">Eye surgery</span> Surgery performed on the eye or its adnexa

Eye surgery, also known as ophthalmic surgery or ocular surgery, is surgery performed on the eye or its adnexa. Eye surgery is part of ophthalmology and is performed by an ophthalmologist or eye surgeon. The eye is a fragile organ, and requires due care before, during, and after a surgical procedure to minimize or prevent further damage. An eye surgeon is responsible for selecting the appropriate surgical procedure for the patient, and for taking the necessary safety precautions. Mentions of eye surgery can be found in several ancient texts dating back as early as 1800 BC, with cataract treatment starting in the fifth century BC. It continues to be a widely practiced class of surgery, with various techniques having been developed for treating eye problems.

<span class="mw-page-title-main">Radial keratotomy</span> Refractive surgical procedure to correct myopia (nearsightedness

Radial keratotomy (RK) is a refractive surgical procedure to correct myopia (nearsightedness). It was developed in 1974 by Svyatoslav Fyodorov, a Russian ophthalmologist. It has been largely supplanted by newer, more accurate operations, such as photorefractive keratectomy, LASIK, Epi-LASIK and the phakic intraocular lens.

<span class="mw-page-title-main">Ciliary body</span> Part of the eye

The ciliary body is a part of the eye that includes the ciliary muscle, which controls the shape of the lens, and the ciliary epithelium, which produces the aqueous humor. The aqueous humor is produced in the non-pigmented portion of the ciliary body. The ciliary body is part of the uvea, the layer of tissue that delivers oxygen and nutrients to the eye tissues. The ciliary body joins the ora serrata of the choroid to the root of the iris.

<span class="mw-page-title-main">Corneal transplantation</span> Surgical procedure of repairing corneal tissue to treat corneal blindness

Corneal transplantation, also known as corneal grafting, is a surgical procedure where a damaged or diseased cornea is replaced by donated corneal tissue. When the entire cornea is replaced it is known as penetrating keratoplasty and when only part of the cornea is replaced it is known as lamellar keratoplasty. Keratoplasty simply means surgery to the cornea. The graft is taken from a recently deceased individual with no known diseases or other factors that may affect the chance of survival of the donated tissue or the health of the recipient.

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<span class="mw-page-title-main">Brimonidine</span> Chemical compound

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<span class="mw-page-title-main">Idoxuridine</span> Chemical compound

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<span class="mw-page-title-main">Corneal neovascularization</span> Medical condition

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<span class="mw-page-title-main">Corneal ulcer</span> Medical condition of the eye

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<span class="mw-page-title-main">Fungal contamination of contact lenses</span>

Microbial corneal infection is the most serious and "most common vision threatening" complication of contact lens wear, which is believed to be strongly associated with contact lens cases. Such infections "are being increasingly recognized as an important cause of morbidity and blindness" and "may even be life-threatening." While the cornea is believed to be the most common site for fungal eye infections, other parts of the eye such as the orbit, sclera, eyelids, and more may also be involved. Contact lens cases are recognized as a "potential source of pathogens associated with corneal ulcers" and according to Moorfields Eye Hospital, contact lens wear is “the most prevalent risk factor for new cases of corneal ulcers.” Contaminants "isolated from contact lens associated corneal ulcers have often been shown to be" the same as found in the patient's contact lens case, thus providing evidence contaminated contact lens cases may be a "replenishable source of pathogenic microbes."

<span class="mw-page-title-main">Herpes simplex keratitis</span> Medical condition

Herpetic simplex keratitis is a form of keratitis caused by recurrent herpes simplex virus (HSV) infection in the cornea.

<span class="mw-page-title-main">Corneal button</span> Replacement cormea for transplantation

A corneal button is a replacement cornea to be transplanted in the place of a damaged, diseased or opacified cornea, normally approximately 8.5–9.0mm in diameter. It is used in a corneal transplantation procedure whereby the whole, or part, of a cornea is replaced. The donor tissue can now be held for days to even weeks of the donor's death and is normally a small, rounded shape. The main use of the corneal button is during procedures where the entirety of the cornea needs to be replaced, also known as penetrating keratoplasty.

<span class="mw-page-title-main">Corneal opacity</span> Medical condition

Corneal opacification is a term used when the human cornea loses its transparency. The term corneal opacity is used particularly for the loss of transparency of cornea due to scarring. Transparency of the cornea is dependent on the uniform diameter and the regular spacing and arrangement of the collagen fibrils within the stroma. Alterations in the spacing of collagen fibrils in a variety of conditions including corneal edema, scars, and macular corneal dystrophy is clinically manifested as corneal opacity. The term corneal blindness is commonly used to describe blindness due to corneal opacity.

Peripheral Ulcerative Keratitis (PUK) is a group of destructive inflammatory diseases involving the peripheral cornea in human eyes. The symptoms of PUK include pain, redness of the eyeball, photophobia, and decreased vision accompanied by distinctive signs of crescent-shaped damage of the cornea. The causes of this disease are broad, ranging from injuries, contamination of contact lenses, to association with other systemic conditions. PUK is associated with different ocular and systemic diseases. Mooren's ulcer is a common form of PUK. The majority of PUK is mediated by local or systemic immunological processes, which can lead to inflammation and eventually tissue damage. Standard PUK diagnostic test involves reviewing the medical history and a completing physical examinations. Two major treatments are the use of medications such as corticosteroids or other immunosuppressive agents and surgical resection of the conjunctiva. The prognosis of PUK is unclear with one study providing potential complications. PUK is a rare condition with an estimated incidence of 3 per million annually.

References

  1. 1 2 "150 Faces of Peddie". 150 Faces of Peddie: 61. Spring 2014.
  2. 1 2 3 4 NEOS (1962). "New England Ophthalmological Society Distinguished Achievement Award".
  3. ↑ Remington JS, Jacobs L, Kaufman, HE (January 1960). "Toxoplasmosis in the Adult". New England Journal of Medicine. 262 (4): 180–86. doi:10.1056/NEJM196001282620406. S2CID   37065768.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. 1 2 3 4 5 6 Charters L (March 1, 2018). "Confessions of an Innovator". Ophthalmology Times.
  5. ↑ Kaufman HE, Martola E-L, Dohlman C (August 1962). "Use of 5-Iodo-Deoxyuridine(IDU) in Treatment of Herpes Simplex Keratitis". Archives of Ophthalmology. 68 (2): 235–9. doi:10.1001/archopht.1962.00960030239015. PMID   14454436.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ↑ Shors T (July 29, 2016). "3.7". Understanding Viruses.
  7. ↑ Kaufman HE, Martola E-L, Dohlman C (Sep–Oct 1963). "Herpes Simplex Treatment with Idu and Corticosteroids". Trans Am Acad Ophthalmol Otolaryngol. 67: 695–701. PMID   14064628.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ↑ Zimmerman TJ, Kaufman HE (1977). "Timolol. A Beta-Adrenergic Blocking Agent for the Treatment of Glaucoma". Archives of Ophthalmology. 95 (4): 601–4. doi:10.1001/archopht.1977.04450040067008. PMID   322648.
  9. ↑ Newmark E, Ellison AC, Kaufman HE. (March 1970). "Pimaricin Therapy of Cephalosporium and Fusarium Keratitis". American Journal of Ophthalmology. 69 (3): 458–65. doi:10.1016/0002-9394(70)92283-X. PMID   4908192.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  10. ↑ Gassett AR, Kaufman, HE (Feb 1970). "Therapeutic Uses of Hydrophilic Contact Lenses". American Journal of Ophthalmology. 69 (2): 252–9. doi:10.1016/0002-9394(70)91287-0. PMID   5414007.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ↑ Bourne WM, Kaufman HE (March 1976). "Specular Microscopy of Human Corneal Endothelium in VIVO". American Journal of Ophthalmology. 81 (31): 319–23. doi:10.1016/0002-9394(76)90247-6. PMID   1258956.
  12. ↑ McCarey BE, Kaufman, HE (March 1974). "Improved corneal storage". Investigative Ophthalmology. 13 (3): 165–73. PMID   4813700.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  13. ↑ Kaufman HE, Varnell ED, Kaufman SC, Beuerman RW, Barron B (August 1985). "K-Sol Corneal Preservation". American Journal of Ophthalmology. 100 (2): 299–304. doi:10.1016/0002-9394(85)90796-2. PMID   3927738.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  14. ↑ "FDA Recall #Z-073-9". FDA Enforcement Document. Oct 11–12, 1988.
  15. ↑ Lindstrom RL, Kaufman HE, Skelnik DL (September 1992). "Optisol Corneal Storage Medium". American Journal of Ophthalmology. 114 (3): 345–56. doi:10.1016/S0002-9394(14)71803-3. PMID   1524127.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  16. ↑ McDonald MB, Kaufman HE, Frantz JM; et al. (May 1989). "Excimer Laser Ablation in a Human Eye". Archives of Ophthalmology. 107 (5): 641–2. doi:10.1001/archopht.1989.01070010659013. PMID   2719572.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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