Surgical innovations in Cataract and Retina Surgery West of the Mississippi
1960 – 2019
Grateful thanks to Dr. Wayne Fung
Foreword – From 1960 to 2019, in the areas of Cataract and Retina surgery, 10 – 12 major developments took place in ophthalmology; for example, the cause and treatment of the Irvine-Gass Syndrome, Laser, Cryosurgery, Phacoemulsification, Vitrectomy, Intraocular Lens Implantation, VEGF, closing of VEGF, heavier than water fluids, gas bubbles used to unroll the retina, and expanding gasses. These advances and the individuals behind them are presented here.
Instrumentation and Innovation
Even from Its earliest days, the Ophthalmology Department at CPMC always had the newest equipment. This was primarily because purchases were not encumbered by state bureaucratic hurdles. For sure, large purchases were made only after budgeting over time, but the time was rarely more than two years. For smaller items, applications were submitted to the Lions Eye Foundation of Northern California and Nevada. This mutually beneficial association was established early 1960. Thus, by 1960 a Zeiss Xenon Arc Photocoagulator was on the Pacific campus. This instrument was the third one produced by Zeiss and the first west of the Mississippi.
This instrument enabled the sealing of retinal tears and holes without submitting the patient to a surgical operation. The procedure was performed after a retrobulbar anesthetic injection and through a dilated pupil. The skill required of the surgeon was locating the pathology deep in the back eye using an awkward direct-type ophthalmoscope.
“Big Bertha” was my favorite name for her. She stood 5 feet tall, 4 feet wide and weighed 400 pounds. Fortunately, she was mounted on wheels, so that with effort she could be placed over the supine patient’s head.
Post treatment, the patient was required to use anti-inflammatory drops and mild dilating drops for five days. The procedure could stimulate and intraocular inflammatory response because the white light was so intense and the iris at the pupil’s edge could be exposed to the energy.
By the mid-sixties, the Photocoagulator was replaced by the Argon Laser.
The three major advantages of the Argon Laser were that the welding spots were smaller, more accurately focused and did not require a pre-treatment anesthetic injection. Thus, merely dropping an anesthetic on the cornea, followed by the placement of a small contact lens on the corner enabled treatment in an office setting.
The Laser Era
With the introduction of laser instrumentation, ophthalmology took another step toward the modern age. It allowed for much more accuracy in focusing and regulating power delivered. The name, “L-A-S-E-R’ is an acronym standing for: Light, Amplification, Stimulated, Radiation. The features about Laser light which allows for precise selection of spot size and accurate focusing are these:
- Selection of precise wave lengths as opposed to full spectrum white light.
- ONLY these photos are pumped into a chamber and bounced back and forth, until –
- The waves are parallel at which point they are released and channeled to target!
The initial laser was the Ruby Laser which was given the name because it produced red light by activating a ruby crystal. This was technically easy, but the goal at the time was to ablate new vessels arising from the optic nerves of diabetic patients. To do this, it was reasoned that the ideal color should be argon green. The hemoglobin of the RBC’s would absorb the green efficiently, and maximally.
Hence, the Argon Laser was developed and when put into practice all planning seemed ideal! The spot size could be narrowed to the width of any vessel arising from the optic disc and the argon green was absorbed by the vessels efficiently. All seemed perfect, except when the treated vessel was rechecked 30 minutes after treatment. What had seemed like an obstructed vessel was actually a segmental spasm in the treated vessel.
It was not discovered until several years later that pan-retinal photocoagulation, or PRP, was the best way to close disc neovascularization via the anti-VEGF pathway. VEGF, or vascular endothelial growth factor will be discussed later.
The Intracapsular Cataract Operation of I.C.C.E.
In the early 1960’s, the standard cataract operation in the country was the intracapsular cataract operation. As the name implies the entire cataract lens was removed from the eye through a 180-degree superior incision extending from 9 o’clock to 3 o’clock!
In the West, the wide wound was closed with three preplaced #6-0 silk mattress sutures. In the East, many areas did not use sutures at all! Spreading the conjunctival flap over the sclera, immobilizing the patient’s head between sandbags and supine bed rest was the order of the day! Hence, patients in the West customarily spent five days and nights in the hospital, while in the East a seven-day stay was more common.
Primary Goals of the operation consisted of the following:
- Remove the entire lens without breaking the lens capsule with capsule forceps, early on, or a cryosurgery tip later.
- Preserve the anterior vitreous face.
- Guard against the corneal endothelial trauma.
- Securely close the superior wound with sutures with as little corneal distortion as possible.
Potential complications included the following, but were not limited to these:
- Infection in the eye (endophthalmitis)
- Post-operative pain from the wound size and sutures: (#3,#6-0 mattress sutures at CPMC)
- Wound leak or rupture
- Visual Distortion, Uncorrected post-operative vision
- Falls, not infrequently resulting in broken hips in the elderly population
- Irvine-Gass Syndrome
- Five nights inpatient (West Coast); seven nights (East Coast)
The “Irvine-Gass Syndrome”
During the era of the I.C.C. E., or the intracapsular-cataract- extraction, a clinical scenario was vexing: During the post-operative period of an apparently successful operation, while central was improving or stabilized, vision would suddenly decline for no apparent reason.
Closer examination of the operated eye would almost always reveal a wick of formed vitreous – coming from the vitreous cavity, extending through the pupil, and adhering to the under surface of the superior wound. A fluorescein angiogram would reveal the declining vision was secondary to cystoid macular edema!
In a multi-centered, prospective clinical trial, several colleagues and I were able to statistically prove that if the peaked pupil were eliminated, the central vision would be restored. The operation consisted of inserting the tip of a micro spatula between the anterior surface of the iris, tunneling under the vitreous wick, or plaque followed by advancing the tip of a guillotine-cutting vitrectomy instrument and eliminating the overlying vitreous until the peaked pupil was eliminated. It was the distortion of the uvea which was responsible for the low-grade inflammation and CME. (Ophthalmology, 89: 898-901, 1982.)
By the late 1960’s, some cataract operations were performed by Phacoemulsification – the use of small-incisions and ultrasound.
There were several major advantages of this method:
- Shorter operating time.
- Less post-operative pain and photosensitivity
- Faster visual recovery
- Less visual distortion (astigmatism)
- Reduced possibility of post-operative wound rupture
- Reduced post-operative topical drops
Charles D. Kelman, M.D. (5/23/1930 – 6/1/2004)
In the 1960’s a Manhattan ophthalmologist, Charles D. Kelman, M.D. aspired to perform cataract surgery through a narrow limbal incision to avoid the complications associated with the wide superior incision of the day. He invented over 100 instruments which would introduce fluid into the anterior chamber, aspirate, any material from the A/C, and various devices to crush, segment, or maserate the lens, but all failed because of trauma to surrounding structures!
As his frustrations mounted, he allowed his personal hygiene to lapse until his close acquaintances pressured him to visit a dentist! During the visit, the dentist scaled his teeth using ultrasound! He asked the dentist what kind of device was being used. The story goes that once he heard “ultrasound”, he rushed out of the office still covered by the protective cape and ran to his lab to investigate!
I was in the second class he conducted to introduce Phacoemulsification to ophthalmology. He charged $1,000 per student for the five-day course. On the last afternoon, he took the students to a local nightclub where he performed on his saxophone with a small combo.
In this setting, Phacoemulsification was not well regarded by academic ophthalmology! But because it was performed carefully, the procedure produced impressive results with far fewer complications.
Intraocular Lens Implantation – Sir Harold Ridley, M.D. (7/10/1906 – 5/25/2001)
By the early 1980’s, following the pioneering work of Sir Harold Ridley, M.D., of the U.K., intraocular lenses were implanted as a routine. This eliminated the use of thick, heavy, vision-distorting, post-operative spectacles and/or contact lenses. The sharp reduction of disastrous falls resulting in broken hips were also a welcome benefit. At CPMC, the implantation of the posterior chamber, haptic-in-the-bag IOL’s became routine.
THE INTRODUCTION OF THE VITRECTOMY ERA
Robert Machemer, M.D. (3/16/1933 – 12/23/2009)
In 1965, Robert Machemer, M.D. completed his residency at the University of Göttingen. After working for two years as an assistant in the University Eye Clinic of Göttingen, he applied for and won a NATO fellowship to come to the U.S. to do research and further his studies.
Because he had his own funding, he visited Harvard, Philadelphia, and Miami. He finally decided to work in Miami at the Bascom Palmer Eye Institute (BPEI) because, as he later stated: “Dr. Norton toughest, and most interesting questions. asked me the toughest, and most interesting questions.
The first research challenge he undertook was developing a technique to reliably create an experimental retinal detachment in young rabbits! Many had tried earlier but failed. But by making a small modification in an essential step, he succeeded. Others had started by loading a syringe with a small amount of Hyaluronic acid, advancing the tip of the needle close to the surface of the retina, and then forcefully injecting the bolus of acid. This routinely created a retinal tear and detachment, but in a day or two, the detachment would spontaneously resettle.
The tiny wrinkle he did to prevent resettling was to mix the acid with the young monkey’s vitreous by push-pulling, push-pulling, repeatedly, until a large pool of liquid hovered over the retinal tear! The presence of a pool of liquid over the tear assured that spontaneous resettling would not occur.
Now, with this reliable model, Dr. Machemer and Duco Hamasaki, Ph.D., an expert in electron microscopy, performed a series of experiments illuminating how the outer segments of the retina rebuild themselves after reattachment.
At this same time, a voluntary faculty person of the BPEI team, David Kasner, M.D., had a private patient who had markedly reduced vision in both eyes secondary to systemic amyloidosis, a rare disease due to the production of amyloid in his bone marrow. Dave wondered, as did everyone at the institute, how well would the eye survive if all the contents of the vitreous cavity were removed? This had never been done before!
After obtaining full consent from the patient, Dave performed an I.C.C.E. followed by an “open-sky-vitrectomy” using Weck sponges and scissors. The patient’s vision improved dramatically and the eye survived! Having witnessed this, Bob began wondering about performing a total vitrectomy, through a pars plana approach!
With the collaboration of Jean Marie Parel Ph.D., a bioengineer, they began to develop an instrument which would aspirate the vitreous, cut the aspirated material with a mortar and pestle rotating cutter, deliver fluid into the vitreous cavity, and illuminate the action with a fiber optic sleeve. The tip of this multifunctional instrument was about 4 mm. Bob named the instrument: “V.I.S.C.”: vitreous, infusion, suction, cutter.
Initially, diabetic patients with chronic, long-standing, whitish-grey material filling their vitreous cavities were stunning successes. The chronic, non-clearing nature of the hemorrhages allowed the vitreous fibrils to be “digested” by the decaying hemoglobin.
Soon, it was learned that vitreous fibrils not associated with long-standing, non-clearing hemorrhages were sometimes difficult to cut. At times it was necessary to introduce a Needle-Knife, like the Ziegler Knife, using one’s left hand to cut the vitreous between the intake-port and the trailing tag of the retina!
In the early 1970’s, Vitrectomy, a surgical procedure performed within the middle of the eye, was begun at CPMC. This was a surgical approach pioneered by Robert Machemer, M.D. of Miami. It enabled surgeons to directly reverse undesirable forces affecting the retina: usually traction forces between the detaching vitreous and the trailing retina.
Because this surgery took place deep in the middle of the eye, the existing operating microscopes (the Zeiss OPMI II) only provided clear views if the front eye was woefully inadequate. To address this need, Zeiss created the OPMI VI and CPMC received one of the earliest models.
In addition to severing traction forces between the vitreous and the retina, this approach enabled removal of retained non-magnetic intraocular foreign bodies, chronic, diabetic vitreous hemorrhages, and idiopathic macular holes.
In the 1960’s, a significant diagnostic tool was introduced to ophthalmology: Fluorescein Angiography. This advance allowed for the photographic examination of the various layers of the back of the eye. Before this, the ten layers of the retina seemed like a single layer of cellophane carrying blood vessels. But by injecting a light-absorbing dye into the arm vein of a patient and continuously photographing the dye as it circulated through the retina, each layer could be examined stereoscopically.
Then in 1991, a further advance occurred which allowed for viewing the retina in cross-section without injecting dye: Ocular Coherence Tomography (OCT).
Shortly after that, it was possible to view the retina and the layer beneath it, the Choroid, through software manipulation and without injecting dye: OCT-A.
The VEGF Era
Age-Related Macular Degeneration of the wet form has been a scourge in ophthalmology for decades. The condition is secondary to the almost overnight appearance of new capillaries beneath the central macula. Hence, a patient losing the ability to read in the eye, overnight, was not an infrequent scenario. When it happens in both eyes it is devastating! Not only is reading vision gone, but driving vision is also impacted.
With fluorescein angiography (early) and OCT-A (later), discovering the cause of the condition was simple. The successful treatment was to take ophthalmology almost four decades!
The disappointing scenario while searching for a cure was as follows:
- The cause was always the sprouting of new capillaries beneath the area of the macula.
- These leaking capillaries could be accurately ablated (sealed) using laser.
- The seal would last weeks, months, or sometimes longer. Vision would improve and sometimes return to normal.
- But invariably, a new set of capillaries would sprout along the treatment scar at a point closest to the central macula, the fovea.
- With each laser recurrence the central macula became more threatened.
- The scenario became so common in practice that lasering across the fovea became acceptable to preserve some central vision.
Moses Judah Folkman, M.D. (1/24/1933 – 1/14/2008)
In 1970, Moses Judah Folkman, M.D. of Harvard University, published a paper in which he theorized that cancerous tumors must exude a substance which stimulates the growth of new blood vessels in order to provide nourishment for its continued growth.
The medical community said this is teleological thinking that needed to be verified, thus implying that he should isolate the substance and purify it!
In his lab at Harvard University, he and his team worked for YEARS until they identified a substance which he called “endothelial growth factor” or VEGF.
Once isolated, it was cloned by Napoleone Ferrara, M.D. at Genentech. Once cloned, Genentech developed two monoclonal antibodies: the first bevacizumab (Avastin), eﬀective against metastatic Colon Cancer, and Ranibizumab, eﬀective against the new vessels responsible for the wet form of age-related macular degeneration and was approved by the FDA in 2016.
To be currently effective, patients must report back to their caregivers approximately every 4 to 6 weeks for repeat injections. To decrease this burden on both the patient and the caregiver, Genentech has developed a reservoir which can be implanted into the anterior vitreous in the region of the pars plana. The application for use is currently before the FDA in its second year of the LADDER trial. The hope is that this device will lengthen the visits to twice a year!
Improvements in Vitreous Surgery
It was Steve Charles, M.D. of Memphis, Tennessee who first suggested separating the infusion and illumination functions of the system. This dramatically reduced the “frontal” dimension of the instrument from one 4.0 mm scleral opening to three 1.0 mm ports: Cutter, infusion, and fiber optic light. Steve was also the one who introduced the idea of internal drainage through the retinal hole, and the fluid gas exchange. Rotary Cutters soon gave-way to Guillotine gutters. The gauge of cutters rapidly minified, to the now 25 and 27 gauges!
My mentor Edward W. D. Norton M.D. introduced the use of intravitreal gas to unroll giant retinal tears.
Stanley Chang, M.D.,
of New York introduced heavier than water intravitreal injections, which allowed for the unrolling of giant retinal tears while the patient was in the supine position.
Acknowledgement: The author would like to express his deep appreciation for the effort placed into this work by Sabrina Romero-Wilson. The placement of the photos and illustrations, the overall “word-smithing”, but especially the unraveling of Pages vs. Word into Google would not have been possible without her!