The evolution of eyes: major steps. The Keeler lecture 2017: centenary of Keeler Ltd.

Ocular evolution is an immense topic, and I do not expect to cover all the details of this process in this manuscript. I will present some concepts about some of the major steps in the evolutionary process to stimulate your thinking about this interesting and complex topic. In the prebiotic soup, vision was not inevitable. Eyes were not preordained. Nor were their shapes, sizes, or current physiology. Sight is an evolutionary gift but it was not ineluctable. The existence of eyes is so basic to our profession that we often do not consider how and why vision appeared or evolved on earth at all. Although vision is a principal sensory modality for at least three major phyla and is present in three or four more phyla, there are other sensory mechanisms that could have been and were occasionally selected instead. Some animals rely on other sensory mechanisms such as audition, echolocation, or olfaction that are much more effective in their particular niche than would be vision. We may not believe those sensory mechanisms to be as robust as vision, but the creatures using those skills would argue otherwise. Why does vision exist at all? And why is it so dominant at least in the number of species that rely upon it for their principal sensory mechanism? How did vision begin? What were the important steps in the evolution of eyes? How did eyes differentiate along their various paths, and why?

Informed consent in senile cataract extraction.

One day after surgery for senile cataract, we interviewed 50 patients to determine what percentage of the preoperative informed consent was retained. No patient felt less inclined to undergo surgery after hearing the informed consent and all patients believed the preoperative explanation had been adequate. This study found retention of relevant information was only 37% when assessed by ten standard questions. Only two (4%) of the patients remembered more than two of the five risks of surgery. Blindness, the most frequently recalled, was known by only 17 (34%). More than 80% failed to recall either hemorrhage (46/50), infection (47/50), failure of the procedure to improve visual acuity (42/50), or death (44/50) as other complications. Only 20% (10/50) would have remembered to protect the operated-on eye. Patients denied prior counseling for four of the ten questions (mean). Factors related to poor retention include advanced age and less than a high school education. Previous cataract surgery, level of anxiety prior to surgery, and the patient's sex did not appear to influence retention.

Incidence of cataract extraction in Pima Indians. Diabetes as a risk factor.

The incidence of visually disabling cataract was estimated by the rate of first cataract extraction in a population of Pima Indians in Arizona. The annual age-specific rates of cataract surgery (first and second eyes) were 3.7 to 5.9 times as high as the estimated US rates. Diabetes was a strong risk factor for first cataract surgery in all age and sex groups except in men aged 75 to 84 years. Overall, with age and sex controlled, the rate of first cataract surgery was 2.2 times as high (95% confidence interval, 1.3 to 3.9) in diabetic as in nondiabetic subjects. Cataract surgery was related to the duration and type of treatment of diabetes. Insulin-treated diabetics had about five times the rate of those with normal glucose tolerance. The rate of cataract surgery was lowest in subjects with normal glucose tolerance, somewhat higher in those with impaired glucose tolerance, and even higher with increasing duration of diabetes.

Leprosy in a trachomatous population.

In an Egyptian leprosy hospital, 17% of 133 patients had a visual acuity of less than 3/60. Corneal opacity, phthisis bulbi, and cataract accounted for 85% of blindness. Leprosy and trachoma together produce blinding corneal opacity by exposure, leprous keratitis, and trichiasis and entropion. Inturned lids, a late result of conjunctival scarring due to childhood trachoma, were less frequent in patients with lepromatous leprosy than in patients with tuberculoid leprosy; because conjunctival scarring from trachoma depends on cell-mediated immunity, patients with lepromatous leprosy may not have had severe trachomatous scarring develop due to their lifelong abnormality in cellular immunity. In patients with leprosy, even when complicated by trachoma, simple measures to prevent or restore vision include medical treatment of leprosy, surgical correction of lid deformities, sector iridectomy for constricted pupils or central corneal opacities, and cataract extraction.

Cataract extraction. Risk factors in a health maintenance organization population under 60 years of age.

Risk factors for cataract extraction in a young (less than 60 years of age) urban health maintenance organization population were evaluated in a case-control study. The subjects (72 case-control pairs) subscribed to the Kaiser Permanente Medical Care Program in the San Francisco Bay area and had cataract extraction between 1976 and 1980. All patients had visual acuity of at least 20/40 OU, documented before development of cataracts. Thirty-six (50%) of the 72 cataract extraction patients had at least one known risk factor for cataract formation, including trauma, intraocular inflammation, diabetes mellitus, syphilis, oral or topical steroid use, or previous eye surgery. Male patients were found to be a mean of 4.3 years younger than female patients, and diabetics were found to be a mean of 3.5 years older than nondiabetics. Variables found to be related to cataract extraction in univariate analysis included diagnosis of diabetes mellitus, a family history of cataracts, pulse rate, white blood cell count, and syphilis.

Ocular leprosy.

Leprosy, also known as Hansen's disease, affects millions of people worldwide and is largely confined to the developing world. Although Hansen's disease is disfiguring, crippling, and even blinding in its later stages, it is not commonly lethal but gradually steals sensory input from the digits and the visual pathways. In this article, the epidemiology and pathogenesis of leprosy are reviewed, with an emphasis on ocular involvement, treatment, and prevention.

The epidemiologic association of Fuchs' heterochromic iridocyclitis and ocular toxoplasmosis.

Between January 1983 and July 1987, I examined 25 patients at the Department of Ophthalmology, West Virginia University, who had the anterior segment characteristics of Fuchs' heterochromic iridocyclitis. Of these patients, 16 had fundus lesions suggestive of ocular toxoplasmosis. Of these 16 patients, 13 had a positive serologic test for toxoplasmosis, two patients were not tested, and one patient had a negative test at 1:16. The remaining nine patients with Fuchs' heterochromic iridocyclitis had no fundus lesions suggestive of toxoplasmosis. A chart review of 792 consecutive patients at the Retinal Unit, West Virginia University, during a six-month period disclosed that 24 of 590 patients (4%) had chorioretinal scars suggestive of toxoplasmosis. I concluded from these data that in at least one subgroup of patients with Fuchs' heterochromic iridocyclitis there is a significant association with the chorioretinal scars of toxoplasmosis (P less than .01), and this is suggestive of a causal relationship.

Epidemiologic aspects of senile cataract extraction stratified by visual acuity, age, and sex.

A review of records for 221 patients 50 years old and older undergoing first cataract extractions showed that women constituted 64% of this population (142 cases). The men had a mean age of 70.8 years and the women a mean age of 71.8 years. This difference was not significant. Men had a significantly (P less than .05) better mean best corrected visual acuity preoperatively than women (20/100 vs 20/400). In the two younger groups (those aged 50 to 59 years and those aged 60 to 69 years), men also had significantly (P less than .05) better preoperative visual acuities.

Interstitial linear keratitis.

A 15-year-old boy and a 21-year-old man had linear, nonmigratory corneal inflammations in the anterior stroma. The recurrent lesions extended from corneoscleral limbus to corneoscleral limbus within the palpebral aperture. They healed spontaneously with some scarring and minimal vascularization but without loss of vision. The cause could not be determined and serologic tests for syphilis were negative in both cases.

Atypical reginal vasculitis associated with ticlopidine hydrochloridine use.

PURPOSE: To describe two cases of retinal vasculitis shortly after the initiation of ticlopidine hydrochloride (Ticlid, Roche, Kingsland St, NJ) therapy. METHODS: Case reports of two patients. The first patient was a 43-year-old white woman complaining of spots, floaters, and flashes of lights in both eyes 3 weeks after the initiation of treatment with ticlopidine hydrochloride. The second patient was a 72-year-old woman complaining of decreased visual acuity in the left eye for 2 weeks, 4 weeks after initiating oral administration of ticlopidine hydrochloride. RESULTS: Both patients had resolution of the vasculitis after the discontinuation of ticlopidine therapy. CONCLUSION: The temporal relation and the resolution of symptoms after discontinuation of ticlopidine hydrochloride suggest that the vasculitis was related to the ticlopidine hydrochloride administration. Knowledge of this potential complication of ticlopidine hydrochloride is important for the early diagnosis of this possible drug-induced side effect and the cessation of ticlopidine hydrochloride.

High-dose intravenous pulse methylprednisolone hemisuccinate in acute Behçet retinitis.

PURPOSE: To report the response of acute Behçet retinitis to high-dose corticosteroids. METHOD: Case report. A 58-year-old man with Behçet disease and severe bilateral glaucoma experienced a sudden decrease of visual acuity to counting fingers in his (better-seeing) left eye. Examination disclosed hypopyon uveitis and an infiltrative retinitis threatening the fovea. He received intravenous methylprednisolone hemisuccinate, 1 gram per hour on each of 3 successive days, followed by oral prednisone and cyclosporine. RESULTS: The retinal infiltrate disappeared within 24 hours. Visual acuity improved to LE, 20/400 by day 5 and returned to LE, 20/30 after 3 months. A visual field demonstrated a scotoma corresponding to the location of the previous retinitis. CONCLUSION: High-dose intravenous methylprednisolone can reverse severe vision loss in acute Behçet retinitis.

Regression of cytomegalovirus retinitis associated with protease-inhibitor treatment in patients with AIDS.

PURPOSE: To report the observation that anti-retroviral therapy that includes a protease inhibitor can induce the regression of cytomegalovirus retinitis without requiring specific anticytomegalovirus drug therapy. METHODS: We examined the fundi of four patients with advanced acquired immunodeficiency syndrome (AIDS) who were placed on highly active antiretroviral therapy consisting of two nucleoside analogs and a protease inhibitor. The combined medications resulted in increased CD4+ T-lymphocyte counts and decreased load of human immunodeficiency virus (HIV-1). A prospective evaluation of the effect of these medications on an active cytomegalovirus retinitis lesion was conducted in one patient. Retinal lesions were documented with fundus photography. RESULTS: None of these patients received specific anticytomegalovirus medications. The average baseline CD4+ T-lymphocyte count was 33 cells per microliter (range, 4 to 88 cells per microliter) and increased an average of 118.5 cells per microliter (range, 66 to 185 cells per microliter). Average baseline plasma HIV-1 viral loads (HIV-1-RNA copies per ml) decreased 1.46 log units (range, 0.65 to 2.93 log units). In one patient, posterior progression (border advancement toward the posterior pole) of a cytomegalovirus retinitis lesion decelerated over time and stopped. Three other patients on initial examination had areas of retinal scarring consistent with healed cytomegalovirus retinitis. CONCLUSIONS: The addition of an HIV-1 protease inhibitor in the treatment of AIDS may lead to complete regression of cytomegalovirus retinitis without specific anticytomegalovirus medications. This effect may be related to reduced HIV-1 loads, a possible direct drug effect, an increase in CD4+ T-lymphocyte counts, or other associated changes in immune status.

Herpes simplex dendritic keratitis after keratoplasty.

We treated three patients with herpes simplex dendritic keratitis that occurred between three and 11 months after keratoplasty. The patients had no history of herpetic infection. The eyes of two of the patients were grafted for corneal scarring of undetermined origin. The eye of the third patient was grafted for pseudophakic bullous keratopathy. At the time of onset of dendritic keratitis, all three patients were receiving either maintenance or higher doses of topical corticosteroids. All infections responded to topical antiviral treatment. The findings in these patients illustrate the importance of considering herpes simplex keratitis in the differential diagnosis of all late-onset epithelial defects in the corneal graft, even in the absence of a history of herpes simplex keratitis.

Simultaneous onset of Vogt-Koyanagi-Harada syndrome in monozygotic twins.

PURPOSE/METHODS: We examined monozygotic twins of Vietnamese ancestry in whom the Vogt-Koyanagi-Harada syndrome developed. RESULTS/CONCLUSIONS: Both patients demonstrated typical clinical findings of the Vogt-Koyanagi-Harada syndrome, and HLA typing disclosed HLA-DR4, an antigen that is present in a disproportionate number of patients with the Vogt-Koyanagi-Harada syndrome. Although familial cases of the Vogt-Koyanagi-Harada syndrome are rare, associations with HLA antigens may indicate that genetic factors play a role in this disease.

Comparison of astigmatism after penetrating keratoplasty by experienced cornea surgeons and cornea fellows.

PURPOSE: We compared surgically induced astigmatism after penetrating keratoplasty performed by supervised cornea fellows and experienced cornea surgeons. METHODS: Data were collected by retrospective chart review of 166 cases (166 eyes) of penetrating keratoplasty: 63 performed by two cornea surgeons and 103 by four cornea fellows. Astigmatism was calculated using scalar and vector methods. Vector analysis was performed on 109 of 166 eyes. Two techniques were compared: intraoperative keratometry and suture adjustment and the torque-antitorque running suture technique with no intraoperative keratometry or suture adjustment. RESULTS: Mean surgically induced scalar astigmatism changed from preoperative astigmatism by 3.27 diopters (fellows) and 2.94 diopters (attending surgeons). In 109 cases, surgically induced vector cylinder changed from peroperative astigmatism by 4.21 diopters at 98 degrees (fellows) and 4.25 diopters at 114 degrees (surgeons). Surgically induced vector astigmatism changed from preoperative astigmatism by 4.67 diopters at 93 degrees in the first 6 months (fellows) and by 3.79 diopters at 103 degrees in the second 6 months. Analysis of x-axis and y-axis components of the surgically induced vector cylinder showed that the majority of the astigmatism was induced in the y-axis and that this difference was significant (P < .001) in all comparisons, independent of technique or surgeon group. CONCLUSIONS: Penetrating keratoplasty performed by supervised cornea fellows resulted in similar rates of surgically induced vector astigmatism, surface asymmetry, and surface regularity as that by experienced surgeons. Fellows induced significantly more with-the-rule astigmatism, but this tendency decreased with further training. Penetrating keratoplasty astigmatic outcomes were not significantly different whether or not intraopertive keratometry and suture adjustment were utilized. This study supports the concept that increased experience with corneal transplantation improves the outcome of penetrating keratoplasty by using the criterion of postoperative astigmatism as a measures.

Social economic development in the prevention of global blindness.

AIMS: To assess the relation between a country's economic developmental status and its prevalence of blindness. METHODS: Available epidemiological data on worldwide visual loss and its causes compiled by the World Health Organization were reviewed. Findings were compared with economic development data from the involved countries and regions. Analysis was completed in view of the socioeconomic status of each country and region. RESULTS: Analysis of the global distribution of blindness indicates a trend of higher prevalence existing in developing countries with lower per capita income. Preventable causes of blindness (that is, cataract, trachoma) are also more prevalent in these countries. CONCLUSIONS: Because economic development is shown to be a factor in blindness, programmes for blindness prevention should not be the only route to the elimination of unnecessary blindness throughout the world. Concomitant economic development is also necessary to reduce and eventually eradicate much of the preventable and avoidable causes of blindness.

Tear hyperosmolarity in renal dialysis patients asymptomatic for dry eye.

Renal dialysis patients have hyperosmolar bodily fluids due to high urea levels, and accordingly their tears should be hyperosmolar. Tear hyperosmolarity is a sensitive and specific test for dry eye. The purpose of this study was to determine whether renal dialysis patients have hyperosmolar tears and dry eye. Ten renal dialysis patients completed the McMonnies and Ho dry eye questionnaire and underwent tear osmolarity testing before dialysis. Serum osmolarity was calculated from serum sodium, potassium, and blood urea nitrogen levels. Half of the subjects also participated in tear osmolarity testing after dialysis and underwent an eye examination that included rose bengal and fluorescein staining, Schirmer's testing, and tear break-up time testing. All of the subjects had both hyperosmolar serum and tears, and tear osmolarities were positive for dry eye in all subjects. However, none of the subjects tested positively for dry eye with the questionnaire. The subjects had some physical findings consistent with dry eye, and Schirmer's testing showed decreased tear production. Renal dialysis patients are a population that have hyperosmolar tears yet remain asymptomatic for dry eye. Urea has been used for years as a dermatologic treatment for dry skin. The high levels of urea in the tears of dialysis patients may protect them from developing dry eye. Tear hyperosmolarity due specifically to ionized solutes such as sodium and potassium is probably more pathogenic in causing dry eye than is hyperosmolarity in general. Nevertheless, tear osmolarity testing should not be used as a dry eye monitor in renal failure patients.

Successful transplantation of bioengineered tissue replacements in patients with ocular surface disease.

PURPOSE: To bioengineer a corneal surface replacement using ex vivo expanded, cultured corneal epithelial stem cells seeded on a matrix derived from amniotic membrane and use this bioengineered graft to manage difficult ocular surface disease. METHODS: Fourteen patients with ocular surface disease unresponsive to standard medical and surgical treatments, including seven patients with presumed limbal stem cell deficiency were chosen for transplantation of a bioengineered composite corneal surface in eye each. Presumed corneal stem cells were harvested from either the patient's or related donor's limbus, expanded ex vivo, and cultivated on a carrier of modified human amniotic membrane. The resulting composite cultured tissue was transplanted to the ocular surface of the diseased eye, from which the abnormal tissue had been surgically removed. Ten patients received autologous grafts, and four received allogeneic grafts. RESULTS: A successful outcome, defined as restoration or improvement of vision, along with maintenance of corneal re-epithelialization and absence or recurrence of surface disease was obtained in 6 of the 10 patients with autologous procedures and in all 4 allogeneic transplants. Follow-up ranged 6-19 months with a mean of 13 months. CONCLUSIONS: This novel technique documents that presumed corneal epithelial stem cells can be harvested safely from the limbus, expanded successfully in vitro, and grown on denuded amniotic membrane. The resultant composite cultured tissue can be transplanted and appears to successfully manage eyes with difficult ocular surface disease, including those with stem cell deficiency. This technique minimizes the threat of damage or depletion to the contralateral or donor limbus.

Single culture media in infectious keratitis.

PURPOSE: To evaluate the usefulness of the various culture media used in the traditional workup in infectious keratitis. METHODS: Microbiology data sheets from all corneal cultures performed at the University of California Davis Medical Center over a 1-year period were reviewed retrospectively. RESULTS: Bacterial cultures were sent in 76 cases. In 19 cases, culture specimens from ulcers were plated onto blood, chocolate, and inhibitory mold agar and were inoculated into an anaerobic medium. In 58 cases, blood and chocolate agar were sent. In 70% of cases, blood and chocolate agar provided identical information. Inhibitory mold agar was positive twice in 39 plates sent. A fungal pathogen had been identified on chocolate agar plates sent for these cases. CONCLUSION: In the evaluation of infectious keratitis, plating onto chocolate agar or blood agar alone is a reasonable alternative to sending multiple cultures.

Corneal storage medium preservation with defensins.

We used a synthetic defensin (rabbit neutrophil peptide-1; NP-1) as a microbicide in a corneal storage medium, Optisol without antimicrobial compounds. We established growth curves in Optisol for Staphylococcus aureus, Streptococcus pneumoniae, and Pseudomonas aeruginosa. Each organism was evaluated separately at 4 degrees C, 23 degrees C, and 37 degrees C in Optisol with NP-1 at each of four different concentrations including 1, 10, 100, and 200 micrograms/ml. When the three organisms were evaluated in Optisol containing NP-1, we found that a concentration of 200 micrograms/ml of NP-1 successfully killed 99.9% (the limits of our assay) of all three organisms at all temperatures tested. We conclude that NP-1 exhibits promise as a nonantibiotic preservative agent in corneal storage media, since it was effective in killing organisms at all temperatures, including 4 degrees C.