Contact lenses induce short- and long-term changes in corneal endothelium. Although the endothelial-bleb response is a short-term change, the long-term changes include polymegethism (variation in cell size) and pleomorphism (variation in cell shape) in endothelial morphology. 1,2
Two possible methods of estimating the degree of polymegethism in the endothelial mosaic are to examine the coefficient of variation (CV) of the cell areas and the ratio of maximum cell size/minimum (Max/Min) cell size. 3–5
It has been shown that polymegethism and pleomorphism increase slightly with age. 6,7 There have also been a number of reports that indicate an increase in endothelial polymegethism and pleomorphism with polymethylmethacrylate (PMMA) hard contact lens, 1,3 soft lens, and extended hydrogel lens 5 wear. However, eyes wearing silicone lenses, which are highly permeable to oxygen, do not develop any change. 8,9 It was suggested that high Dk/L lenses, which provide more oxygen to the cornea, might induce less prominent changes. 10–12 Polymegethism that occurs with contact lens wear is probably due to chronic corneal hypoxia, or the inflammatory response of the cornea related to the synthesis by the cytochrome P-450 arachidonic acid metabolites, 13,14 and the extent of polymegathous change is related to both the oxygen transmissibility of the lenses worn and the length of lens wear.
We decided to perform a follow-up study with daily-wear RGP fluorocarbon contact lens wearers, with a greater oxygen permeability (Dk=92×10−11), to record the morphologic changes which occur in the corneal endothelium. The endothelial cell density changes of the same subject group were discussed before. 15
MATERIALS AND METHODS
A total of 57 contact lens wearers (97 eyes) were selected from the Department of Ophthalmology at Trakya University Hospital. Subjects who had a history of previous contact lens wear, ocular trauma, inflammation, diabetes, glaucoma, keratoconus, or anterior segment surgery were excluded.
Informed consent was obtained from each subject prior to study. A routine ophthalmic examination (ie. history, keratometer, refraction, slit lamp examination, tonometry, fundus examination) and Schirmer test were performed on each subject before beginning the study.
The same type of RGP contact lens with high oxygen permeability (Persecon92E, Ciba Vision) was adapted for all subjects. The specifications of the lens parameters are shown in Table 1. A trial lens fitting (beginning with 0.1 mm flatter than the flat curvature of cornea) was then performed on each subject to obtain good centralization and sufficient movement by parallel fluorescein pattern.
Each subject began with 2 hours for 1 week, during which at least 14 hours per day of comfortable wear was achieved. After this adaptation period, the subjects began daily wear.
Endothelial photographs were taken of each eye at the initial phase of the study as the baseline for the appearance of the corneal endothelium. The study lasted for 1 year, including 1-week, 1-month, 3-months, 6-months, and 1-year follow-up visits. A contact lens wear history was taken detailing the average number of hours of daily wear in every control. During each visit, noncontact specular microscopy of the central corneal endothelium was performed using a Topcon SL-5D biomicroscope, and endothelial photographs were obtained. Five average photographs were taken for each cornea. To obtain photographs from a defined and reproducible area on the central cornea, the patients fixated at a small target placed on the biomicroscope. The endothelium was viewed at ×176 magnification because of the specifications of the specular microscope and photographed with 400 ASA Ilford HP5 film at ×15 magnification in the film plane. The films obtained were projected on a white plane, resulting in ×330 magnification. Each film was examined carefully, and the best three photographs of five, with good cell boundaries, for each eye in every time period were used. All the cells in the 2×12 cm (24 cm2) pattern were then evaluated. The long axis of the largest cell and the long axis of the smallest cell were measured by a micrometer on the wall, and the ratio of maximum cell size-to-minimum cell size was obtained for every three films. The average of the three ratios (Max/Min) was expressed as the ratio of max cell size/min cells size of the sample as an index of polymegethism. Cell shapes were evaluated by noting the number of apices of each cell. This was achieved by counting the apex of each cell and then reporting the relative frequency of 5-, 6-, and 7-sided cells in the monolayer (pleomorphism).
The operator was unaware of the names of patients and dates of the examination when pointing out or counting the cells on films.
Subjects were divided into six groups according to the RGP contact lens wearing time. These groups were matched by the same eye of the subject prior to contact lens wear.
Paired Student’s t test and Pearson correlation analyses were used in statistical analysis by using the Number Crunching Statistical System (NCSS) software program. A two-tailed probability of 0.05 or less was considered statistically significant.
Ninety-seven eyes of 57 subjects (18 males, 39 females; mean age 22.7 ±7.8 years, range 12–55 years) participated in the study. Seventeen subjects were using a contact lens only in one eye because of anisometropia, and the other 40 subjects were using in both eyes.
During each visit, a detailed history of the daily wearing time schedule (14 hours/day) was obtained and the average total wearing time was found to be 1636 ± 1794 hours.
During the 1-year observation period, the attendance of the study group dropped from 97 to 23 eyes, and the remaining eyes were divided into six groups according to the duration of contact lens wear.
There was no significant difference between the mean age of the six groups (P >0.05) (Table 2).
The refractive error of the eyes ranged from −28.00 to +9.50. Fifty-nine eyes (60.8%) had myopia, 20 eyes (20.6%) had high myopia (≥7.00 diopter[D]), 18 eyes (18.6%) had hyperopia and in 47 eyes (48.5%) there were ≥1 D astigmatism.
Endothelial photographs of subjects prior to RGP contact lens wear (baseline) were evaluated. Max/Min cell-size ratio and the relative frequency of 5-, 6-, and 7-sided cells were calculated (Table 3).
A significant positive correlation between age and Max/Min cell-size ratio was found (this meant that polymegethism increases with age [r =0.29, P =0.003]).
No significant correlation was found between age and the relative frequency of 5-, 6-, and 7-sided cells (r =0.11, P =0.28;r =−0.15, P =0.12;r =0.13, P =0.18).
All groups were matched by the same eye of the subject before contact lens wear.
During the 1-year period there was a significant gradual increase in Max/Min cell size ratio (Fig. 1)(Table 4).
There was an increase in the relative frequency of 5-sided cells during the period of RGP contact lens wear, but this increase was not statistically significant (Table 5).
A statistically significant gradual decrease in the relative frequency of hexagonality during the period of RGP contact lens wear was found (Table 6).
There was a statistically significant difference between the relative frequency of 7-sided cells during the period of RGP contact lens wear. In the first week, there was a significant increase in the relative frequency of 7-sided cells and this statistically significant result was similar throughout the 1-year period. (Table 7).
It has been shown in various studies that as the cornea ages, polymegethism and pleomorphism increase slightly. 6,7 In our study, a significant positive correlation between age and Max/Min was found. This means that polymegethism increases with age (r =0.29, P =0.003). Typically, with aging, the polymegathous endothelium shows a larger population of small and large cells. While there was a negative but insignificant correlation between age and the relative frequency of hexagonality (r =−0.15, P =0.12), a positive but insignificant correlation between age and the relative frequency of 5-sided and the 7-sided cells was found.
It was reported with low Dk RGP lenses that corneal hypoxia occurred, and the corneal endothelial layer shifted from a pattern of uniformly sized cells to a layer of large and small cells and resulted as a variation in cell size (polymegethism) and shape (pleomorphism). 16,17
An increase in polymegethism was shown in various studies with different Dk’s (Dk from 4.6–96) RGP contact lens wear. 2,10,12,18,19 Carlson et al, 2 studied RGP contact lens wearers (Dk/L differs from 4.6–17.3) for 2 to 7 years. A significant increase in polymegethism was reported in contact lens wearers compared with the control group. Liberman et al, 19 showed an increase of polymegethism under the extended wear of fluoro-silicon methacrylate lenses (nominal Dk=96) after one year. Polse et al, 12 noted an increase in polymegethism compared to nonwearers after 6 months of RGP contact lens wear (Dk=55). Orsborn et al, 10 studied six subjects wearing four different types of RGP contact lens material (Dk=16–57) and after 3 months showed an insignificant increase in polymegethism in the daily wear eyes. Bourne et al, 18 followed 19 new wearers with daily-wear RGP fluorocarbon contact lenses (Dk from 30–70) for 3 years. An increase in the CV of cell area was shown 2 months after lens fitting and increased further over the subsequent 3 years. We found a significant increase in Max/Min as an indicator of endothelial polymegethism in response to daily wear of RGP contact lens, which is in agreement with these studies. In our study, it was documented that the polymegethic changes began in the first week after lens fitting and significantly increased further over 1 year.
Pleomorphism is defined as a long-term corneal endothelial cell shape change due to contact lens wear. It was reported that cellular hexagonality is a more sensitive indicator of endothelial damage or instability than the CV of cell size. The percentage of hexagonal cells making up the endothelial mosaic decreases in hard, soft, and extended wear contact lens wearers, and there is a compensatory increase in cells of other than six sides. 1
A decrease in hexagonal cells was noted after daily wear of RGP lenses for 1 year. 20–21 Orsborn et al, 10 studied six subjects wearing RGP contact lens material (Dk=16–57) and after 3 months showed an insignificant decrease in percent frequency of hexagonal cells in the daily wear eyes. Bourne et al, 18 followed up 19 new wearers with daily wear RGP fluorocarbon contact lenses (Dk from 30–70) for 3 years. The percentage of hexagonal cells decreased at each examination during these 3 years, but the decrease from baseline was statistically significant only after 1 year of wear. There was a weak but significant correlation between Dk/L and the change from baseline in percentage of hexagonal cells at 2 months.
We found a significant gradual decrease in relative frequency of hexagonal cells and a significant increase in 7-sided cells beginning from the first week after lens fitting and up to 1 year. The maximum decrease in hexagonal cells was 9% at the end of the first year. An increase in percent frequency of 5-sided cells throughout the follow up period was demonstrated, but this was not significant.
Nieuwendal et al 11 reported no significant change in cell size (polymegethism) and cell shape (pleomorphism) with permanent wear of rigid high Dk-lenses (nominal Dk 71 or 92) in 32 eyes of 16 subjects after 7 to 24 months; however, only 9 of the subjects had not worn any contact lens previously. Carlson et al 2 followed up RGP contact lens wearers for a period of between 2 and 7 years. No significant change in pleomorphism was noted in contact lens wearers compared to the control group. Ogihara et al 22 found no change in the percentage of hexagonal cells after daily wear for 3 months. These results are not in agreement with our study. Polymegethic and pleomorphic changes in endothelial cells show great individual variations, and in RGP contact lens wearers these changes occur less frequently than in hard, and soft contact lens wearers. So, a large number of subjects should be studied with RGP contact lenses to establish these small changes. On the other hand, sample sizes are very small in studies with RGP contact lenses. 2,8,10–12,22,23 We considered that aforementioned studies could not be demonstrated statistically due to their inadequate sample sizes. The second explanation may be that we get the Max/Min cell size as indicator of polymegethism, so Max/Min ratio is perhaps a more sensitive indicator than CV for polymegethism.
In conclusion, although oxygen transmissibility in fluorocarbon contact lenses has improved over previous hard and soft contact lenses even in the daily wear schedule, polymegethism and pleomorphism are still induced within 1 week and seem to increase over 1 year. A long follow up, with more specified sample sizes are necessary and the physiologic effect of increase in percent frequency of 5- and 7-sided cells on corneal metabolism should be studied.
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Keywords:© 2002 The Contact Lens Association of Ophthalmologists, Inc.
Rigid gas-permeable contact lenses; Specular microscopy; Corneal endothelium; Polymegethism; Pleomorphism