Rate Of Endothelial Cell Loss Research Articles

Initial results of endothelial cell counts after Artisan Lens for Phakic Eyes: An evaluation of the united states food and drug administration ophtec study

Purpose To evaluate the endothelial cell count change in eyes implanted with the iris-claw phakic Artisan lens for treatment of moderate to high myopia. Design Prospective, multicenter clinical trial. Participants The first 765 eyes enrolled at 25 North American sites in the United States Food and Drug Administration Ophtec clinical trial of the myopic Artisan IOL. Outcome analyses of endothelial cell count measurements were based on those obtained before surgery and at 6, 12, and 24 months after surgery performed between October 1998 and December 2001. Setting Multiple private and university practices. Methods Percentage change in endothelial cell count from baseline to 6, 12, and 24 months were analyzed using specular microscopy. Upper limit of detecting endothelial cell density change was estimated using 3 repeated counts at preoperative and postoperative time frames. Main outcome measures Percentage change in endothelial cell loss. Results The mean preoperative endothelial cell count was 2631±442 cells/mm 2. Percentage change from baseline at 6, 12, and 24 months was −0.09%±16.39%, −0.87%±16.35%, and −0.78%±17.41%. No statistically significative postoperative endothelial cell loss was found. The endothelial cell loss rate was higher among patients who wore spectacles before surgery and was correlated negatively with preoperative endothelial cell density ( P<0.001). No relationships were noted between endothelial cell loss and either patient age or implant power. A 4.1% repeatability of measurements was found based on the average of 3 repeated counts, whereas single cell count estimates were associated with a 23% accuracy in detecting endothelial cell density change. In a worst-case scenario, adjusting for measurement accuracy, 9% of all eyes were at higher risk of a 10% loss of cell density at 12 months after surgery, although eyes at higher risk were found to have high preoperative endothelial cell counts ( P<0.0001). Conclusions The Artisan iris-claw phakic intraocular lens did not result in significant loss of endothelial cell density up to 2 years after implantation of the myopic Artisan phakic lens.

Corneal endothelial damage and its repair after phacoemulsification

To introduce a grading system for corneal edema after phacoemulsification and to study the corneal endothelial damage and its repair after phacoemulsification. One hundred and five senile cataracts after phacoemulsification were included. Corneal edema was categorized into grades 0 to 4. Endothelial densities at various locations of the cornea were measured with specular microscopy before and three months after surgery. The corneal endothelial cell loss rate was 4.6%, 14.9%, 40.8%, 67.0% and 84.4% in eyes with corneal edema from grades 0 to 4, respectively. Time required for resolution of corneal edema was (2.1 +/- 0.7) days (grade 1), (5.6 +/- 1.9) days (grade 2) and (21.8 +/- 7.1) days (grade 3). The endothelial cell densities at superior, mid and inferior portions of the cornea were (2006 +/- 546) cells/mm(2), (1979 +/- 545) cells/mm(2) and (1754 +/- 543) cells/mm(2) respectively at 3 months after phacoemulsification. Postoperative endothelial cell loss at superior, mid and inferior portions of the cornea was (627 +/- 496) cells/mm(2), (656 +/- 492) cells/mm(2) and (1026 +/- 509) cells/mm(2) respectively. The difference in postoperative endothelial cell densities between the superior and inferior portions of the cornea was statistically significant (P = 0.017), so was the difference between mid and inferior portions of the corneas (P = 0.027). There was no statistically significant difference between the superior and mid portions of the cornea (P = 0.867). The grading system for corneal edema is helpful in evaluating the severity of endothelial damage after phacoemulsification and can be used to predict the outcome of the cornea. The major area of endothelial injury after phacoemulsification occurs at the inferior portion of the cornea.

This Issue of Acta

There are many important scientific original papers in the current issue. In the first one Reinhard and coworkers studied endothelial cell loss after penetrating keratoplasty. Two hundred and thirty-three patients were divided into three classes depending on the degree of HLA matching between donor and recipient. It is known that proper HLA matching decreases the risk of immune reactions after keratoplasty. Despite this, and somewhat surprising, the authors found that better HLA matching was not associated with lower rates of endothelial cell loss than groups with more mismatches. This paper and histocompatibility and grafting in general are discussed in the Guest Editorial by Ehlers. There are two epidemiological papers in this issue of Acta. Bergman et al. performed a highly unusual prospective study of a representative population sample between 70 and 97 years of age in Gothenburg. The subjects were examined at age 70 in 1971, and then again at ages 82, 85, 95 and 97. The study sheds new light on visual function at higher ages. At 82 years 20% of subjects demonstrated decreased vision, defined as visual acuity ≤0.5. At 97 years of age 80% had reduced visual function. Reduced blood folate levels, smoking and high BMI correlated with reduced visual acuities at higher ages. The study clearly shows that ‘normal VA’ is age dependent, but also raises questions about what the requirements should be for defining a normal subject at very high ages. The other epidemiological study published in the current issue also deals with visual acuity. This Inter99 study has been conducted in Copenhagen. Very different age groups have been studied and in this, much younger, population, the most important cause of visual impairment was strabismic amblyopia. Myopia was twice as common in subjects with a university degree as in those without such a degree. Quality of life has very properly come into the focus of ophthalmic researchers. Chabert and coworkers studied the influence of uveal melanoma diagnosis and therapy on QoL. Their results are encouraging; compared to patients with other types of cancer patients with uveal melanoma had relatively satisfactory QoL levels, that were also not seriously reduced by radiotherapy. Fledelius and coworkers present two papers dealing with retinopathy of prematurity. The first one has a provoking subtitle: Has progress reached a plateau? This suggestion by the authors – that ‘the apparent progress in the fight against ROP over many years seems to have come to a halt’– agrees with the impression of many ROP specialists, and is a challenge for specialists in neonatology and ophthalmologists working with premature infants. The accompanying paper presents epidemiological county-based ROP data; one of the differences was a ROP frequency of 31% in 1998–2001 compared to only 10% in the preceding 4-year period. Despite the suggested worsening the authors propose a lowering of gestational age and birthweight limits for ROP screening. Fechtner and coworkers present results from two large 3-month randomised studies with altogether 544 patients comparing Xalatan and Cosopt. There was no difference in IOP-lowering efficacy between the two treatment alternatives. Ocakoglu et al. measured optic nerve head and peripapillary blood flow with the Heidelberg flowmeter in 22 patients with unilateral exfoliation syndrome and 30 age-matched controls. The exfoliation eyes had lowest blood flow, but flow was also somewhat lower in the nonexfoliative fellow eyes than in the normal controls. Exfoliations have been shown to be an independent risk factor for glaucoma damage, and reduced blood flow in exfoliation eyes has, of course, often been considered a possible explanation. In a study of vigabatrin-treated patients using a novel type of visual field testing Frisén reports perimetric deficits that were proportional to the total dose of vigabatrin. There are two papers about pterygium in this issue of Acta. In a retrospective study Frau and coworkers report very positive surgical results in 104 patients operated with corneo-conjunctival autografts. They saw no recurrences at all. In a study from Jordan Al-Bdour and coworkers studied risk factors for this condition. Sun exposure was the most important risk factor, and the authors recommend preventive measures. There are two experimental studies in the current issue. Wasselius et al. studied Cystatin C in the rat and mouse, and found a striking similarity of localization of Cystatin C and cathepsin B, indicating that in the eye the former substance may be a regulator of the latter. Lin and coworkers found a significant association of p21 codon 31 polymorphism and POAG in China. The Diagnosis/Therapy in Ophthalmology section shows an unusual case of an isolated metastasis to the eye from a gastric adenocarcinoma. In the current issue there are also three case reports, all worth reading, on morning glory syndrome (cf. the cover illustration!), on telangiectasis in optic disc maculopathy, and on ERG abnormalities after methotrexate therapy, plus – as always – a number of interesting letters.

Quantification of rat retinal growth and vascular population changes after single and split doses of proton irradiation: translational study using stereology methods.

This study quantified architectural and population changes in the rat retinal vasculature after proton irradiation using stereology. A 100 MeV conformal proton beam delivered 8, 14, 20 and 28 Gy as single and split doses to the whole eye. The vascular networks were prepared from retinal digests. Stereological methods were used to obtain the area of the retina and unbiased estimates of microvessel/artery/vein endothelial, pericyte and smooth muscle population, and vessel length. The retinal area increased progressively in the unirradiated, age-matched controls and in the retinas irradiated with 8 and 14 Gy, indicating uniform progressive retinal growth. No growth occurred after 20 and 28 Gy. Regression analysis of total endothelial cell number in all vessels (arteries, veins and capillaries) after irradiation documented a progressive time- and dose-dependent cell loss occurring over 15 to 24 months. The difference from controls was significant (P<0.01) after 28 Gy given in single and split doses and after 20 Gy given as a split dose (P<0.05). Total vessel length in microvessel was significantly shortened at 20 and 28 Gy compared to that of controls (P<0.05). No evident dose recovery was observed in the endothelial populations after split doses. At 10 Gy, the rate of endothelial cell loss, a dose parameter used to characterize the time- and dose-dependent loss of the endothelial population, was doubled.

Corneal endothelial cell protection during phacoemulsification: Low- versus high-molecular-weight sodium hyaluronate

Purpose To compare the efficacy of low- and high-molecular-weight sodium hyaluronate in protecting corneal endothelial cells during phacoemulsification. Setting Miyata Eye Hospital, Miyakonojo, Miyazaki, Japan. Methods One hundred forty-nine eyes of 136 cataract patients were randomly assigned to have cataract surgery using sodium hyaluronate 1% with a low molecular weight (0.6 to 1.2 million d, Opegan®) or sodium hyaluronate 1% with a high molecular weight (4 million d, Healon®) during phacoemulsification. Each group was divided into 2 subgroups depending on the amount of ultrasound (% min) used during phacoemulsification, which was defined as the mean phacoemulsification energy (%) multiplied by phacoemulsification time (minutes). Corneal endothelial cell density was examined preoperatively and 3 months after surgery. The rate of cell loss was compared between the subgroups in the Opegan group and the Healon group. Results In the subgroups with ultrasound of 50% min or less, the mean rate of endothelial cell loss 3 months after surgery was 3.2% ± 4.1% (SD) in the Opegan group and 5.9% ± 5.3% in the Healon group ( P = .0214). In the subgroups with ultrasound over 50% min, the mean rate of endothelial cell loss 3 months after surgery was 7.5% ± 10.6% in the Opegan group and 14.8 ± 9.0% in the Healon group ( P = .0029). Conclusions The results suggest that Opegan is more effective than Healon in protecting corneal endothelial cells during phacoemulsification regardless of the amount of ultrasound energy used.

Efficacy and safety of the soft-shell technique in cases with a hard lens nucleus

Purpose To evaluate the efficacy and safety of the soft-shell technique in reducing corneal endothelial cell damage during cataract surgery in patients with a hard lens nucleus. Setting Miyata Eye Hospital, Miyakonojo, Miyazaki, Japan. Methods Sixty eyes of 57 cataract patients with a hard lens nucleus (Emery-Little classification grade 3 or higher) had phacoemulsification using the soft-shell technique with Healon ® (sodium hyaluronate 1%) and Viscoat ® (sodium hyaluronate 3.0%–chondroitin sulfate 4.0%) (soft-shell group) or with Healon alone (control group). The visual acuity, intraocular pressure (IOP), flare intensity in the anterior chamber, central corneal thickness, and corneal endothelial cell density were evaluated postoperatively. Results There were no significant IOP elevations in either group. The mean central corneal thickness in the control group was 539 μm ± 26.0 (SD) preoperatively and 578 ± 52.0 μm 1 day after surgery; the increase was significant ( P = .0154). There was no significant change in the central corneal thickness in the soft-shell group. There were no statistically significant differences between the 2 groups in uncorrected visual acuity, best corrected visual acuity, IOP, flare intensity in the anterior chamber, and central corneal thickness throughout the follow-up. The rate of endothelial cell loss 3 months after surgery was 6.4% ± 9.6% in the soft-shell group and 16.3% ± 9.8% in the control group ( P = .0003). Conclusion The results suggest that the soft-shell technique is safe and effective in protecting corneal endothelial cells during cataract surgery in patients with a hard lens nucleus.

Phakic intraocular lenses and refractory lensectomy for myopia.

Phakic intraocular lens implantation (IOLs) and clear lens extraction for high to extreme myopia have grown in popularity recently as a consequence of potentially unsatisfactory results with corneal refractive surgery in higher ranges of refractive errors. The refractive outcome of these alternative modalities has been encouraging to date, yet the potential for significant complications exists. Current evidence shows that the risk of retinal detachment after clear lens extraction for myopes is high. Trials with angle-supported phakic IOLs revealed unacceptable rates of pupillary ovalization, IOL rotation, and endothelial cell loss. Iris-fixated and posterior chamber phakic IOLs have proven sufficient safety, but long-term follow-ups of current cohorts are still to be awaited. The implantation of either of the latter two phakic IOLs followed by laser in situ keratomileusis or photorefractive keratectomy (bioptics) provides another option in refractive surgery for high ametropia.

Long-term evaluation of endothelial cell loss after phacoemulsification.

To check whether three months' follow-up is sufficient to determine endothelial cell loss after cataract surgery and whether this value depends on preoperative central endothelial cell density. A two-year prospective assessment of central endothelial cell density was done in 60 eyes after phacoemulsification. In 30 eyes a 3.5 mm corneal incision closed with a single crossed suture was made, and the other 30 had a 3.5 mm scleral tunnel no-stitch incision. Central endothelial cell density was measured before surgery and 1, 3, 6 months and 2 years after. The mean rate of endothelial cell loss even two years after surgery was significantly higher than the physiological rate, amounting to 0.9% per year. There was no correlation between preoperative central endothelial cell density and postoperative cell loss. Even two years' follow-up is not sufficient to establish the total endothelial cell loss after cataract surgery. The amount of cell loss does not depend on the preoperative density.

Comparison of corneal endothelial changes after use of different adjuncts during lens implantation

To evaluate postoperative changes in corneal endothelial cell density, we conducted a retrospective study in 34 patients (35 eyes). Patients underwent extracapsular cataract extraction and posterior chamber lens implantation using an air bubble (23 eyes), sodium hyaluronate (Healon) (6 eyes), or air bubble plus sodium hyaluronate (6 eyes). The endothelial cell density of all eyes decreased from 2496±341 cells/mm2 preoperatively to 1539±371 cells/mm2 1 month postoperatively. The endothelial cell loss rate was 21%, 31%, and 29% in the air bubble, sodium hyaluronate, and air bubble plus sodium hyaluronate groups, respectively (P>.05).

Long-term follow-up of Leiske closed-loop anterior chamber intraocular lenses

Purpose To provide long-term follow-up on the rates of endothelial cell loss in eyes with retained closed-loop anterior chamber intraocular lenses (IOLs). Setting Private practices, Chicago, Illinois, USA. Methods In 1980 to 1982, 3 surgeons performed 587 intracapsular cataract extractions with implantation of Leiske closed-loop anterior chamber IOLs. During the prospective part of the study from 1991 to 1996, 59 patients with 83 eligible eyes were followed using specular microscopy and pachymetry. The mean follow-up of the prospective study was 41.9 months, or 12.9 years from the original cataract surgery. Results No specific preoperative or postoperative factor except the behavior of the fellow eye ( P = .022) predicted the rate of endothelial cell loss. During the prospective study, 6 patients required IOL exchange and corneal transplantation. The rate of corneal decompensation was heavily dependent on the initial measurement of endothelial cell density. Corneas with initial endothelial cell counts greater than 1000 cells/mm 2 had a decompensation rate of 1.5%, and corneas with counts of 500 cells/mm 2 or less had a decompensation rate of 57.1% ( P < .01). Conclusions Clinical examination and serial measurements of endothelial cell density provide the most reliable methods for monitoring patients with closed-loop anterior chamber IOLs. Endothelial cell counts can predict the rate of corneal decompensation. Patients with endothelial cell counts greater than 1000 cells/mm 2 usually do not require an IOL exchange.

Initial endothelial cell density and chronic endothelial cell loss rate in corneal transplants with late endothelial failure

Objective To determine when corneal transplants develop the decreased endothelial cell density that predisposes to late endothelial failure (LEF). Design Noted cohort study within a prospective case series. Participants The authors compared 21 grafts that developed LEF with the remaining transplants (controls) in a longitudinal cohort study of 500 consecutive penetrating keratoplasties by 1 surgeon. Eyes regrafted during the study, fellow eyes of bilateral cases, and patients who did not want their data used for research purposes were excluded, leaving 389 grafts in 389 patients for analysis. Intervention Penetrating keratoplasty. Main outcome measures Endothelial cell density before surgery and at 2 months and 1, 3, 5, and 10 years after surgery. Results Grafts with LEF had lower median endothelial cell densities than other grafts, both before surgery (2710 cells/mm 2 vs. 2991 cells/mm 2; P = 0.02) and 2 months after surgery (1895 cells/mm 2 vs. 2501 cells/mm 2; P < 0.001), a difference that was maintained through 5 postoperative years. Despite having lower preoperative cell densities, the grafts with LEF had larger median endothelial cell losses 2 months after keratoplasty (31% vs. 16%, P = 0.002). The endothelial cell loss subsequent to the 2-month examination, however, was not increased in the grafts with LEF. Risk factors for developing LEF included a low endothelial cell density before surgery ( P = 0.007) and 2 months after surgery ( P = 0.002), aphakia or pseudophakia ( P = 0.04), older recipient age ( P = 0.002) and older donor age ( P = 0.03), and occurrence of an endothelial rejection episode ( P = 0.03). Conclusions Corneal grafts with LEF, the major cause of graft failure after 5 postoperative years, fail from low initial endothelial cell density rather than an increased rate of chronic postoperative cell loss. Improved techniques of corneal preservation should decrease the rate of LEF. In addition to low preoperative and 2-month postoperative endothelial cell density, a higher risk of LEF is also seen in patients with aphakia or pseudophakia, older recipient age, older donor age, and occurrence of an endothelial rejection episode.

Ten-year postoperative results of penetrating keratoplasty

Objective To investigate the changes in central corneal endothelial cells and corneal thickness in transplanted corneas from 5 to 10 years after grafting. This study also aimed to investigate the development of glaucoma, graft rejection, and graft failure during the first 10 postoperative years. Design/participants Longitudinal cohort study of 500 consecutive penetrating keratoplasties by 1 surgeon. Patients were asked to return for follow-up examinations at 2 months and at 1, 3, 5, and 10 years after grafting. The authors excluded eyes regrafted during the study and the fellow eyes of bilateral cases, leaving 394 grafts in 394 patients for analysis. Intervention Penetrating keratoplasty was performed. Main outcome measures Using specular microscopy, the authors measured endothelial cell density, coefficient of variation of cell area, percentage of hexagonal cells, and corneal thickness. The authors performed clinical examinations to determine graft rejection or failure and the development of glaucoma. Results By 10 years postkeratoplasty, 80 of the 394 patients had died and 68 grafts had failed. Of the remaining 246 patients, 119 (48%) returned for their 10-year examinations. For the 72 patients who returned for all of the scheduled postoperative visits and had no rejection episodes, reoperations, or failure, endothelial cell loss from preoperative donor levels at 10 years was 67 ± 18% (mean ± standard deviation), endothelial cell density was 958 ± 471 cells/mm 2, coefficient of variation was 0.32 ± 0.11, hexagonal cells were 56 ± 12%, and corneal thickness was 0.58 ± 0.05 mm. The 5- to 10-year changes for all these values were significant ( P ≤ 0.004). The mean rate of late endothelial cell loss from 5 to 10 years postkeratoplasty was 4.2% per year. Eyes that were aphakic after grafting had the lowest endothelial cell loss (57 ± 24%) and the lowest interval cell loss from 5 to 10 years postkeratoplasty (4 ± 19%). Eyes that were phakic had the highest endothelial cell loss (73 ± 8%) and 5- to 10-year-interval cell loss (17 ± 31%). Eyes with posterior chamber lenses had a greater endothelial cell loss (71 ± 9%) than did eyes with anterior chamber lenses (51 ± 25%, P = 0.03). The 10-year cumulative risk of glaucoma, rejection, or failure was 21%, 21%, and 22%, respectively. Late endothelial failure became the major cause for graft failure, accounting for 9 of the 11 failures after 5 postoperative years. Conclusions From 5 to 10 years after penetrating keratoplasty, the annual rate of endothelial cell loss was seven times the normal rate. The endothelial cell loss, pleomorphism, polymegethism, and corneal thickness increased significantly during this time, indicating continued endothelial instability and dysfunction, resulting in an increasing rate of late endothelial failure.

Preservative-free lidocaine 1 % anterior chamber irrigation as an adjunct to topical anesthesia

Purpose: To evaluate the effect on the central corneal endothelium of anterior chamber irrigation with preservative-free lidocaine 1 % as an adjunct to topical anesthesia during phacoemulsification.Setting: Department of Ophthalmology, Hospital Capuchos, Lisbon, Portugal.Methods: This prospective, randomized, controlled study comprised 59 eyes. Thirtyone eyes had phacoemulsification (in-the-bag cracking technique) under topical anesthesia with anterior chamber irrigation by preservative-free lidocaine 1%. Twenty-eight eyes having the same procedure but with local-regional anesthesia served as the control group. All eyes had preoperative and postoperative specular microscopy and computer-assisted morphometry. A Student's t-test was used for between-group comparison of the following parameters: patient age, central corneal endothelial cell loss, mean endothelial cell size variation, and phacoemulsification ultrasound time. Follow-up was 4 weeks.Results: The between-group differences in mean patient age and ultrasound time were not significant. The differences between groups in the endothelial cell parameters were also not significant. Mean postoperative endothelial cell loss was 3.59% ± 2.79 (SD) in the topical anesthesia group and 4.37 ± 2.00% in the control group. Mean variation in cell size was 3.71 ± 1.57% and 3.79 ± 1.07%, respectively.Conclusion: Intracameral infusion of preservative-free lidocaine 1 % had no effect on the corneal endothelial cell loss rate or mean cell size variation in this short-term assessment.

Single-hook Extraction of the Lens Nucleus

Objective: To introduce and evaluate a new method of extracting the lens nucleus in extracapsular cataract extraction. Study Design: Detailed description of surgical procedures including large anterior capsulotomy, hydrodissection, luxating and extracting the lens nucleus using the Sinskey hook, and observation of intra- and postoperative complications. Setting: Department of Ophthalmology at Shizuoka Red Cross Hospital, Shizuoka, Japan. Patients: Four hundred consecutive patients with cataract undergoing this surgical procedure. Main Outcome Measures: Video monitoring during surgery. Follow-up of three months or longer, and measuring pre- and postoperative corneal endothelial cell density. Results: No intra- or post-operative complications. Corneal endothelial cell loss rate was 5.8% on average at the third postoperative month. Conclusion: Single-hook extraction is a simple and safe procedure for removing the nucleus in extracapsular cataract extraction.

Long-Term Endothelial Cell Loss Following Phacoemulsification: Model for Evaluating Endothelial Damage After Intraocular Surgery

Newer concepts of phakic intraocular lens (IOL) surgery present concerns as to their long-term deleterious effect on the endothelium. We examine the behavior of the endothelium for up to 6 years following uneventful phacoemulsification surgery, to establish a baseline for what might be an acceptable level of endothelial cell loss due to intraocular surgical trauma. Ninety-three eyes undergoing phacoemulsification surgery who had multiple endothelial specular microscopy examinations for up to 6 years were examined. Central endothelial specular photomicrographs were analyzed in all cases and the percent of endothelial cell loss as a function of time was calculated. Cell density calculations were corrected for the normal endothelial cell loss as a function of age. Routine uncomplicated phacoemulsification surgery demonstrated a 9% endothelial cell loss 1 year postoperatively. This is in marked contrast to the 16% average endothelial cell loss cited in the literature after phakic AC-IOL surgery. In general, anterior chamber IOL surgery following cataract removal compares unfavorably to posterior chamber IOL insertion long term (20% cell loss versus 12% cell loss). A model is proposed to look at the rate of endothelial cell loss that would be significant enough to create the threat for corneal edema long term following refractive intraocular surgery in young patients. Suggestions for critical comparisons between the observed endothelial aging seen with phakic IOLs and values for more routine IOL surgery are proposed to predict the long-term threat for endothelial cell loss and corneal decompensation, which might result many years after phakic refractive IOL surgery.

Double Circular Capsulotomy and Intercapsular Phaco-emulsification

We performed a new surgical technique termed double circular capsulotomy and intercapsular phaco-emulsification, in which both the advantages of a circular capsulotomy and intercapsular surgery are utilized. This technique consists of three stttteps: (1) small circular capsulotomy is performed with a diameter of about 3 mm; (2) intercapsular phaco-emulsification is performed between the capsules with the tip inserted through the small capsulotomy opening; (3) a large circular capsulorhexis is performed before lens implantation. As a result, complete in-the-bag fixation can be obtained as capsular integrity is maintained. The mean rate of endothelial cell loss is only 3.9% including hard cases. This double circular capsulotomy and intercapsular phaco-emulsification technique is a very promising method for advancing small incision surgery.

Cell Population Kinetics in Atherogenesis Cell Births and Losses in Intimal Cell Mass‐Derived Lesions in the Abdominal Aorta of Swinea

Atherosclerotic lesions may arise in a number of different ways. The two most notable, perhaps, are by monocyte infiltration of the intima and by hyperplasia of normally occurring intimal cell masses. This report is limited to the ICM-derived lesion type induced by a hyperlipidemic diet in the abdominal aorta of swine. The HL diet results, by 49 days, in accumulation of lipid in about 50% of the ICM cells and increases in cell division activity, as indicated by tritiated thymidine LI fourfold greater than in ICM of control swine. Cell numbers are not significantly increased over controls at 49 days, but by 90 HL diet days, they have increased to eightfold over control values. Throughout the 90 days, about 95% of the cells in the ICM or ICM-lesions are smooth muscle cells. Monocytes appear to constitute no more than 5% of the cells. Calculated lesion cell deaths are small during the 90 days, and foci of necrosis are rarely found. By scanning electron microscopy, the endothelial cell integrity appears to be maintained even over the ICM-lesions at 90 days. Calculations from tritiated thymidine LI indicate endothelial cell losses equivalent to 50% of the LI, but they are not significantly greater for the HL swine than for controls. We suggest, then, that the lipid in the ICM (or something associated with it) is the most likely candidate for the SMC growth stimulatory agent accounting for the increased tritiated thymidine LI and the great increase in ICM-lesion cell numbers between HL diet days 49 and 90. Platelet- and/or monocyte-derived growth factors may also be involved in some subtle fashion, but this study provides no positive evidence to support this hypothesis. Progression of the ICM-derived lesions to the advanced atheromatous phase by 300 days on HL diet appears to be a much more complex process. By 300 days in the specific experiment cited, approximately 65% of the atherosclerotic lesion volume consisted of lipid-rich calcific necrotic debris; calculated death rates of lesion cells were very high compared to that at 90 days; calculated endothelial cell loss rates were considerably higher than in controls; and, large numbers of monocyte-macrophages were present in many areas generally associated with necrotic foci. These changes in the aggregate suggest a much more complex mode of pathogenesis for progression to advanced stages than for initiation and early development.

Specular microscopy with intraocular lens implantations

Specular microscopy performed six months postoperatively on 122 lens implant patients showed that endothelial cell loss rates varied according to method of cataract extraction and type of lens implant. Phacoemulsification with implantation of a Platina-style lens was associated with the highest cell loss; planned extracapsular cataract extraction with implantation of a Choyce-style or J-loop lens was associated with the lowest cell loss. The presence of marked striate keratopathy on the first postoperative day was directly related to endothelial cell loss.

Population dynamics of arterial cells during atherogenesis: IX. Similarity of endothelial cell loss over intimal smooth muscle cell masses (cushions) in aortas of swine fed normolipidemic and hyperlipidemic diets for 60 days

The objective of this study was to ascertain whether the previously demonstrated increased endothelial cell loss over swine aortic intimal cell masses (cushion areas) was dependent on a hyperlipidemic diet being fed to the swine. Aortic endothelial cells were labeled with tritiated thymidine. Fifteen swine were placed on a lowcholesterol (mash) diet for 15 days, at which time five were sacrificed for baseline studies. Five of the remaining swine were continued on the mash diet while five were placed on a hyperlipidemic diet; these two experimental groups were killed on Day 75 of the experiment. The rate of endothelial cell growth, division patterns, and loss of labeled endothelial cells over intimal cell mass and non-intimal cell mass areas were calculated in the two groups by comparing the findings in these groups to the baseline group. While endothelial cell loss was greater over aortic intimal cell mass areas than over other parts of the aorta, the hyperlipidemic diet did not enhance this during the period of study. Endothelial cells were lost at a similar rate over intimal cell mass areas in both the normolipidemic mash group and the hyperlipidemic group. The hyperlipidemic diet did, however, produce a significant increase in the surface area of aorta occupied by intimal cell mass areas, presumably due to the effect of the diet on smooth muscle cells. The endothelial cells covering these areas also increased significantly in number. The increase was brought about by an increase in the number of dividing endothelial cells which more than equaled a decrease in the average number of progeny per endothelial cell.

Population dynamics of arterial cells during atherogenesis: VII. Comparison of loss of endothelial cells over abdominal aortic intimal cellular masses (ICM) with that over non-ICM areas in swine fed a hyperlipidemic diet for 60 days

One of the earlies events in the development of an intimal atherosclerotic lesion may be an alteration in the endothelial cell barrier, allowing the entry of injurious or mitogenic substances, resulting in proliferation of arterial smooth muscle cells. Intimal smooth muscle cell proliferation in atherosclerosis appears to begin in intimal cellular masses (ICM), which are normally occurring intimal structures made up of 2 to 10 layers of smooth muscle cells found predominantly in relation to branching points of arteries. If endothelial cell loss is a precursor of overt atherosclerotic lesions, the loss should be greater over ICM than over areas showing no ICM. This study presents evidence suggesting that in swine the endothelial cell barrier is compromised over intimal cell masses more than in non-ICM regions prior to development of overt atherosclerotic lesions. The method used was to label swine aortic endothelium and ICM using tritiated thymidine. All swine were then placed on a low-fat, low-cholesterol diet for 15 days, at which time five baseline animals were sacrificed; the remaining five were placed on a hyperlipidemic (HL) diet and sacrificed 60 days later. The rate of endothelial cell growth, division patterns, and loss of labeled endothelial cells in the HL swine was determined by comparing the findings in this group with the baseline group. Smooth muscle cells of ICM and non-ICM medial regions were similar in regard to labeling indices in the baseline swine and in regard to division patterns in 60-day HL diet swine, except one which was an active lesion. None of the remaining ICM were active lesions and thus were suitable for study of the covering endothelial cells in what can be assumed to be the prodromal stage of lesion development. The approximate area of the abdominal aorta occupied by intimal cell mass was considerably more than we had anticipated, averaging more than 20%. The labeling indices and endothelial cell division patterns over ICM and non-ICM in the baseline swine were similar. In contrast, the labeling index was lower, and grain count changes indicated more endothelial cell divisions over ICM areas than over non-ICM areas in the hypercholesterolemic swine. Calculation showed that the percentage of endothelial cell loss over ICM in the HL swine was more than twice as great as endothelial cell loss over non-ICM areas. The results of this study suggest the possibility that in the assumed prodromal phase of experimental aortic atherosclerosis in young swine, the endothelial cell barrier may be compromised selectively over areas of predilection for the future development of atherosclerotic lesions. This occurs before there is any evidence of focal increase in intimal smooth muscle cell proliferation, which we regard as the earliest detectable stage of lesion development.