|Year : 2004 | Volume
| Issue : 2 | Page : 133-8
Corneal Endothelial Safety of Intracameral Preservative-free 1% Xylocaine
Alpesh R Shah, Rasesh P Diwan, Abhay R Vasavada, Manzoor Qadir Keng
Iladevi Cataract & IOL Research Centre, Ahmedabad, India
Alpesh R Shah
Iladevi Cataract & IOL Research Centre, Ahmedabad
Source of Support: None, Conflict of Interest: None
Purpose : To evaluate the effect of intracameral preservative-free 1% xylocaine on the corneal endothelium as an adjuvant to topical anaesthesia during phacoemulsification and Acrysof foldable IOL implantation.
Material & Methods: This is a prospective, controlled, randomised, double-masked study. 106 patients with soft to moderately dense (Grade 1-3) senile cataract and corneal endothelial cell density of >1500/mm2 were randomised to the xylocaine group (n=53) and control group(n=53). Central endothelial specular microscopy and ultrasound corneal pachymetry were performed preoperatively. On the first postoperative day the eyes were evaluated for corneal oedema and Descemet's folds. Ultrasound corneal pachymetry was performed at 1, 3 and 12 months. Specular microscopy was performed at 3 and 12 months. Cell loss was expressed as a percentage of preoperative cell density. Six patients could not complete one year follow-up. Chi-square and paired t test (2 tail) statistical tests were applied for analysis.
Results: Four (7.54%) patients in the xylocaine group and 5 (9.43%) in the control group had a few Descemet's folds associated with mild central stromal oedema. Corneal thickness increased from 549.3µ ± 37.2µ to 555.5µ ± 36.5µ in the xylocaine group and from 553.1µ ± 36.2µ to 559.3µ ± 40.5µ in the control group at the one-month postoperative visit. Thickness returned to the preoperative level in xylocaine group 549.6µ ± 34.5µ and control group 554.7µ ± 41.1µ at three months. (P=0.484) The percentage of cell loss was 4.47 ± 2.53% in the xylocaine group and 4.49 ± 3.09 % in the control group at one year. (P=0.97)
Conclusion: Intracameral preservative-free 1% xylocaine does not appear to affect corneal endothelium adversely during phacoemulsification.
Keywords: Topical anaesthesia, phacoemulsification, intracameral xylocaine, endothelial specular microscopy, ultrasound corneal pachymetry
|How to cite this article:|
Shah AR, Diwan RP, Vasavada AR, Keng MQ. Corneal Endothelial Safety of Intracameral Preservative-free 1% Xylocaine. Indian J Ophthalmol 2004;52:133
Topical and intracameral anaesthesia are new options for pain management in phacoemulsification. Injection of anaesthetic agents has been associated with complications such as ocular perforation, retrobulbar heamorrhage, retinal vascular occlusion, optic nerve trauma and extraocular muscle malfunction., Topical anaesthesia has advantage of rapid visual recovery after phacoemulsification. Topical anaesthesia for cataract surgery, popularised by Fichman, has been in use since 1992. Though peribulbar anaesthesia gives akinesia, phacoemulsification can be performed satisfactorily without inducing akinesia. Topical anesthesia has gained wide acceptance as an effective, efficient, practical and safe form of ocular anaesthesia for clear corneal phacoemulsification. ,,,,,,,,,,,,,
The survey of members of the American Society of Cataract and Refractive Surgeons (ASCRS) in 2000 revealed an increase in the use of topical anesthesia to 49% of surgeons from 5% in 1995 and 45% in 1999.
However, topical anaesthesia alone may not work in certain cases because of pain and discomfort arising from frequent pressure changes during phacoemulsifi-cation. Gills suggested preservative-free 1 % xylocaine for intracameral anaesthesia to control intraoperative discomfort. Since the introduction of intracameral anaesthesia in cataract surgery, many investigational and clinical studies have verified its safety postoperatively. ,,,,,,,,,
Nevertheless, some authors advise caution with the use of intracameral anaesthetic agents because of their possible toxic effects on intraocular structures, in particular damage to the corneal endothelium. ,, Changes in the ultrastructure of corneal endothelial cells and an increase in polymorphism and cellular oedema have been reported. Such alterations also occur with preservative-free 1% xylocaine, the concentration most often used for intracameral anaesthesia in cataract surgery. 
This study evaluated the longterm effect of intracameral preservative-free 1% xylocaine on endothelial cell loss after phacoemulsification with foldable IOL implantation in Indian eyes and compared the endothelial cell loss rate with that following topical anaesthesia alone.
This study assessed the safety of intracameral xylocaine. The efficacy of such anaesthesia will be addressed in a separate study.
| Material and Methods|| |
This is a prospective, controlled, randomised, double- masked study. It comprised 106 patients scheduled for phacoemulsification under topical anaesthesia operated between April 2000 and September 2000. Patients with soft to moderately dense senile cataract (Grade 1 to 3 on a scale of 1 to 5) and corneal endothelial cell density of > 1500/mm2 were included in the study. Obese and short-necked patients were also included. Patients with hard cataract (grade 4 and 5), uveitis, glaucoma, previously operated eye, a single eye and white mature cataract were excluded. Patients with diabetes, hypertension and those with whom communication could not be established, for reasons such as hearing disability or language barrier were also excluded.
Patients were evaluated for visual acuity on Snellen's chart, intraocular pressure [IOP] and anterior segment pathology. The endothelium was examined by slit lamp with 16 X magnification for changes like guttatae. Fundus examination was done with direct and indirect ophthalmo-scope. Specular microscopy photographs of the corneal endothelium were taken with a Konan SP 8000 noncon ROBO specular microscope (Konan Medical, Inc, Japan). The endothelial cell density (CD) was estimated counting cell numbers by a computer assisted measuring system after 100 cells in a cluster. Cell density is one of the most important indices. The inherent sampling errors and errors in assessment of cell density are generally within 10% of actual cell density. Cell density of 2000 cells/mm2 or more is considered normal. Other specular parameters noted were coefficient of variation (CV) and hexagonal cells (6A). The maximum and minimum cell area give the range of variation in cell size. The standard deviation of the cell size from the mean is a measure of polymegathism.. The coefficient of variation is calculated by dividing the standard deviation of the cell area by the mean cell area. It is a dimensionless index which gives a measure of polymegathism independent of cell size. The variation in cell shape or pleomorphism is another indicator of corneal health. Cell shapes are described by the number of apices of each cell. The percentage of hexagonal cells is a quantitative measure of pleomorphism. The specular microscope is programmed to select a central location which can be confirmed by a highlighted mark on the monitor. This central location was standardised in all patients. However, it is possible that measurements were not taken at exactly same location. Ultrasound corneal pachymetry (Humphrey Instruments Inc.) was done in the center of the cornea by advising the patient to look at the fixation light. Once again there was a possibility of missing the same point every time.
Using the envelope method patients were randomly assigned to receive either 0.2 ml preservative-free 1% xylocaine (xylocaine group) or BSS (control group). The surgeon and observer were masked to the randomisation The technique of anaesthesia and surgery was standardised. All surgeries were performed under topical anaesthesia. 4% xylocaine (ASTRA IDL Ltd., India) was instilled twice at intervals of 5 minutes during preoperative preparation. Xylocaine was reinstilled just prior to the placement of the temporal corneal incision and also before enlargement of incision for intraocular lens implantation. This technique was followed in all cases. Additional supplementation for breakthrough pain during surgery was given based on the surgeon's subjective impression when the patient complained of pain. If wound integrity was suspected, supplementation with topical 4% xylocaine was avoided just prior to intraocular lens insertion.
Surgeries were done by a single surgeon (ARV) with Alcon Legacy 20000 series (Alcon Labs, Fortworth, USA) phacoemulsifier using 30° Kelman microtip. After making a 3.5 mm three-planed temporal corneal tunnel, either 0.2 ml. preservative-free 1% xylocaine (Sunways Ltd; India) or BSS was injected in the anterior chamber through main tunnel. After 20 seconds, 2% HPMC (Viscomet, Unimed Technologies Ltd; India) was injected. Anterior capsulorhexis was performed under methylcellulose followed by hydrodissection and rotation of nucleus. Our phacoemulsifi-cation technique includes initial sculpting followed by step-by-step chop-in situ and lateral separation and stuffing of nucleus fragment with the stop, chop, chop and stuff technique. Cortex removal was done with a single automated irrigation and aspiration probe. AcrySof MA30BA (Alcon Labs, Fortworth, USA) was implanted in the bag after incision enlargement. Intraoperative details like average phaco power, total phaco time and total infusion fluid volume were noted. Cumulative dissipated energy (CDE) was calculated using the formula:
Average phaco power x Total phaco time
Postoperatively, eyes were evaluated for presence or absence of corneal oedema and Descemet's folds. Quantifi-cation of aqueous flare and cells were made using Hogan's criteria. Intraocular pressure and visual acuity were also recorded. Eyes were examined on day 1, at 1 week and 1, 3, 6 and 12 months postoperatively. Ultrasound corneal pachymetry was performed at 1, 3 and 12 months. Endothelial specular microscopy was performed at 3 and 12 months and parameters like cell denstiy, coefficient of variation and hexagonal cells were recorded. All the readings of specular microscopy and corneal pachymetry were performed by a single observer to avoid bias, both pre and postoperatively. We used a non-contact specular microscope because it is quick and user friendly. Cell loss was expressed as a percentage of preoperative cell density. Chi-square and paired t Test (2 tail) were applied for statistical analysis.
| Results|| |
Six patients could not complete more than 6 months of follow-up as four had to travel a considerable distance and two died during the period. Average follow-up was 13.4 months (range 12.0 to 14.6 months). Demography, preoperative intraocular pressure, infusion fluid volume used and cumulative dissipated energy are comparable in both groups as shown in [Table - 1]. Four (7.54%) patients in xylocaine and 5 (9.43%) patients in control group had a few Descemet's folds associated with mild central stromal oedema on first postoperative day. All corneas had cleared at the one week visit. Uveal inflammatory response as noted on first postoperative day was not statistically significant (P=0.662). IOP on first postoperative day was on an average of 14.4 ± 2.8 mmHg in xylocaine group and 14.4 ± 3.6 mmHg in control group (P=0.895) [Table - 2]. Three patients in xylocaine group had an IOP of 32, 28, 27 mmHg respectively. These patients on second postoperative day had an IOP of 14, 17, 15 mmHg with Timolol maleate 0.5% eye drops twice a day. Similarly in the control group, four patients had an IOP of 30, 29, 24, 23 mmHg. On second postoperative day IOP recorded was 17, 15, 18, 14 mmHg respectively with Timolol maleate 0.5% eye drops twice a day. Best spectacle visual acuity at one year was >6/12 in 48 (90.57%) patients of the xylocaine group and 47 (88.67%) patients of the control group (P=0.646). The other two patients of the xylocaine group had 6/18 best spectacle visual acuity due to age related macular degeneration (ARMD). In the control group two patients with ARMD had 6/18 and one with amblyopia had 6/24 best spectacle visual acuity. As shown in [Table - 3] pachymetry readings at 1 month postoperative visit are higher than preoperative value and are comparable at 3 month postoperative visit. Specular parameters and percentages of cell loss are shown in [Table - 4], [Table - 5] and [Table - 6]. Percentage of cell loss is comparable in both groups at the 3 and 12-month postoperative visit. No patient needed conversion to injection anaesthesia. No patient developed serious complications such as posterior capsule rupture, vitreous loss or zonular dialysis.
| Discussion|| |
Topical anaesthesia for phacoemulsification has gained popularity since the introduction of clear corneal incisions. Better understanding of phacodynamics, improved surgical skill and use of foldable IOLs also have helped popularise topical anaesthesia. Globe manipulation can be done easily to the surgeon's comfort during surgery under topical anaesthesia. It is particularly valuable in cases of one eyed patients as all possible complications of peribulbar and retrobulbar anaesthesia are avoided. Selection criteria would vary from surgeon to surgeon. Preoperative counseling and intraoperative communication improve the surgical performance and the final outcome.
Topically applied xylocaine effectively penetrates the eye through the cornea and can be found in aqueous humour at levels that involve analgesic activity. But in patients with anxiety and complicated ocular history so also as in cases of prolonged surgical time, topical anaesthesia alone may not be sufficient. Pressure changes induced by sudden deepening of the anterior chamber during phacoemulsification are more frequent in young individuals, high myopic and in post vitrectomised eyes. In situations like these intracameral xylocaine has been found beneficial. Intracameral xylocaine appears to act by two mechanisms.
(1) "Uveal anaesthesia" - decrease the sensation induced by stretching of iris root, cliliary body and zonules during inflation-deflation of globe.
(2) Decrease sensitivity to microscope light by anaesthetic effect on the retina-ganglion cell-optic nerve complex.
Studies have shown that high concentrations intracameral xylocaine (2% or 4%) are toxic to the corneal endothelium and cause corneal oedema., 1% xylocaine hydrochloride is safe., A survey of ASCRS members in 2000 revealed that 82% of the surgeons using topical anesthesia used it in combination with intracameral preservative-free 1% xylocaine. This study addresses the longterm safety of intracameral xylocaine.
We have included soft to moderately dense cataracts (Gr. 1 to 3). As the effect of hard cataract emulsification on endothelium is multifactorial, we have excluded grade 4 and 5 cataracts.,, We also feel that the effectiveness of the drug could be different in diabetic and hypertensive patients.
The average age in this study is consistent with our clinical experience. Total infusion fluid volume and phaco energy used in both groups were comparable. CDE and infusion fluid volume were acceptable to our result of phacoemulsification in normal senile cataract under topical anaesthesia. [Unpublished data]
Flare and cells response in immediate postoperative period was acceptable in both groups.
There was short-term rise of the IOP in 3 (5.66%) patients of the xylocaine group and in 4 (7.54%) patients of the control group. The glaucoma was controlled with topical timolol maleate 0.5% and no patient required longterm anti-glaucoma medications. We could not explain the increase in IOP in these patients. They did not have exaggerated postoperative inflammatory response and there was no history of glaucoma in any patient.
The changes produced in endothelium cell density, hexagonality and coefficient of variation in cell area are informative in evaluating the safety of new agents for intracameral use., Preoperative specular parameters and pachymetry were comparable in both xylocaine and control groups. Though preoperative cell density is less than other reported studies, it represents the cell density in the Indian population.
In our study, 4 (7.54%) eyes in xylocaine group and 5 (9.43%) eyes in control group developed Descemet's folds and mild central stromal oedema on first the postoperative day. As genesis of oedema near the incision is multifactorial, we decided to focus on central corneal oedema. All corneas cleared within a week. Percentages of cell loss in our study are within the range reported by other authors.,,, There was no significant difference in specular parameters both pre and postoperatively in patients who developed corneal stromal oedema compared to the patients without stromal oedema postoperatively. Pachymetry gives useful information of the endothelial function. As reported in previous studies,,, corneal thickness returns to the preoperative level by 3 months postoperatively.
A few studies reported in the literature had a study design similar to ours with xylocaine and control groups. All these studies did not report any significant change on the study eyes with intracameral xylocine. ,,, Several other studies have used injection anaesthesia as a control group. These studies also did not show any significant endothelial cell loss in the study or the control eyes. ,,
The study by Heuermann et al with follow-up of 20 months reported that longterm postoperative endothelial cell course with topical anaesthesia combined with intracameral injection of preservative-free 1% xylocaine is a safe alternative to peribulbar anaesthesia. Similarly, our study evaluated longterm endothelial cell loss and found no statistically significant differences between topical anaesthesia combined with intracameral preservative-free 1% xylocaine (xylocaine group) and topical anaesthesia with injection of BSS (control group) one year after surgery.
Although we have not done fundus fluorescein angiography, there was no evidence of macular oedema on fundus examination. There was no evidence of phototoxicity.
In summary, intracameral preservative-free 1% xylocaine does not appear to affect the corneal endothelium adversely during phacoemulsification
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[Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5], [Table - 6]
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