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 Table of Contents    
ORIGINAL ARTICLE
Year : 2017  |  Volume : 10  |  Issue : 3  |  Page : 155-161  

Minimal duration cataract surgery with oblique limbal stab incision technique


Department of Ophthalmology, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India

Date of Web Publication5-Oct-2017

Correspondence Address:
Deepti Mahajan
Department of Ophthalmology, Indira Gandhi Medical College, Shimla, Himachal Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ojo.OJO_76_2015

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   Abstract 

PURPOSE: Small incision cataract surgery (SICS) and phacoemulsification with oblique limbal stab incision technique were studied and compared.
SETTING: The study was conducted in the Department of Ophthalmology, Indira Gandhi Medical College, Shimla, for 1 year.
DESIGN: This was a prospective randomized study.
METHODS: One hundred patients undergoing SICS (6–7 mm) were compared with another age- and sex-matched 100 patients undergoing phaco (2.8 mm) surgery with oblique limbal stab incision technique. These two groups were further subdivided into two groups of 50 each. Patients with traumatic cataract, corneal diseases, and preoperative astigmatism >1.5 D were excluded from the study. The patients were subjected to standard preoperative evaluation. Follow-up was done at 1, 2, 4, 6, and 12 weeks.
RESULTS: Mean surgically induced astigmatism at 12 weeks was <1 D in both groups (+0.62 D ± 0.34 in Group A and +0.46 D ± 0.39 in Group B) (statistically significant P < 0.0010). Mean surgical duration was 690.09 s in SICS and 792.29 s in phacoemulsification (statistically significant, P < 0.0010). Visual outcome was between 6/6 and 6/9 in 86% of the patients in Group A and 97% of patients in Group B at 12 weeks.
CONCLUSION: SICS and phacoemulsification with this technique yield lesser astigmatism than clear corneal and scleral incisions, with the advantage of extension without suturing in complicated cases of phaco and in patients with rigid intraocular lens phacoemulsification gives better BCVA in a larger proportion of patients at 12 weeks.

Keywords: Limbal, oblique, phacoemulsification, small incision cataract surgery, stab incision


How to cite this article:
Mahajan D, Sharma RL, Chaudhary KP. Minimal duration cataract surgery with oblique limbal stab incision technique. Oman J Ophthalmol 2017;10:155-61

How to cite this URL:
Mahajan D, Sharma RL, Chaudhary KP. Minimal duration cataract surgery with oblique limbal stab incision technique. Oman J Ophthalmol [serial online] 2017 [cited 2019 May 21];10:155-61. Available from: http://www.ojoonline.org/text.asp?2017/10/3/155/216015


   Introduction Top


Manual small incision cataract surgery (MSICS) is a technique of extracapsular cataract extraction (ECCE) in which cataract extraction and intraocular lens (IOL) implantation are performed through a suture less, self-sealing valvular sclerocorneal tunnel incision. “Small” in the title refers to the wound being relatively smaller than an ECCE although it is still markedly larger than a phaco wound. It retains most of the advantages of phacoemulsification but can be delivered at a lower cost. It has come as a boon to fill the yawning gap between high cost, high tech phaco machine, and conventional large incision ECCE.

The MSICS is possible without application of superior rectus suture and construction of conjunctival flap. Elimination of these two steps will not only reduce the duration of surgery (minimal duration cataract surgery [MDCS]) but also have other advantages such as better, early healing, and lesser scarring. These modifications to the conventional technique will further refine the SICS and altering the position of incision to astigmatic neutral position makes this technique at par with phaco surgery. Minimal postoperative congestion, minimal scarring, and astigmatism are the final outcome of surgery.[1]

There are differences in the healing effects of incisions at the limbus and the cornea.[2] Limbal incisions appear to heal more quickly and are more resistant to deformation pressure than those in the cornea. Clear corneal incisions also appear to increase the likelihood of visual threatening endophthalmitis.[3] The clear corneal incision has the advantage of better anterior chamber (AC) approach during surgery, but its limitation becomes apparent when it needs enlargement, either for implantation of rigid IOL or in complicated surgery, where suturing will be required and astigmatism will be significant. Similarly, scleral incision has the advantage of lesser induced astigmatism, infections, despite large incision. However, it makes surgery difficult, particularly in hard cataracts, smaller pupil, and deep set eyes.

The sclerocorneal tunnel gives the advantages of both the approaches with lesser induced astigmatism and better AC manipulations. Hence, this study was taken up to compare the MDCS with oblique limbal stab incision in SICS and phacoemulsification.


   Methods Top


This study was carried out in 200 patients with 100 SICS (Group A) and 100 phaco (Group B). Each group was further subdivided into two groups of 50 each for right (A1, B1) and left (A2, B2). One hundred patients undergoing oblique incision (6–7 mm) cataract surgery were compared with another age- and sex-matched 100 patients undergoing phaco (2.8 mm) surgery. Cases with complicated cataract, corneal diseases, preoperative – astigmatism more than 1.5 D were excluded from the study. The patient were subjected to standard preoperative evaluation such as visual acuity (VA), slit lamp examination, IOP recording, fundus examination, keratometery, and biometry. Keratometery was done to know the astigmatism and cylindrical axis as most of the eyes had hazy media due to cataract. The procedure was studied in terms of astigmatism, visual outcome, surgical duration, surgeon comfort, patient comfort, and complications.

Technique

All surgeries was performed under local anesthesia using peribulbar block with 6–8 ml of 2% xylocaine with adrenaline (1 in 2 lac) (Astra–Zenecia Pharma India Ltd.,) and hyaluronidase (50 IU/ml) (Hynidase, Shreya Life Sciences Pvt. Ltd.,) using a 25 mm long 24 G disposable needle. All the surgeries were performed by a single experienced eye surgeon.

  • Stage 1: Direct stab incision: After application of wire speculum, the incision was given directly with keratome (2.8 mm) through the limbal conjunctiva, where it was firmly adhered with the episclera, without superior rectus, conjuctival flap, and cauterization. The tip of keratome was inserted just posterior to the limbus and slowly pushed through the limbal tissue [Figure 1]. Once the tip reached in the cornea, the forward force was reduced and knife was slightly elevated initially to move along the corneal curvature and later dipped down into the AC to make a sharp and straight entry. The optimal incision depth was usually one-half of the thickness of the limbus or about 0.3–0.4 mm. The length of the tunnel was 2.8 or 3.2 mm depending on the blade and breadth was kept with a similar proportion, respectively [Figure 1]. The shape of external entry incision was straight or slightly curved and that of internal entry was straight. The position of stab incision was oblique in superotemporal quadrant in right eye and superonasal in left eye taking 10:30 clock hour of limbus as center point.
    Figure 1

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  • Stage 2: From entry into anterior chamber till nucleus delivery [Figure 2]
    Figure 2: Steps of minimal duration cataract surgery

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  • Stage 3: Delivery of nuleus till subconjuctival application [Figure 2].


The optimal incision depth was usually one-half of the thickness of the limbus or about 0.3–0.4 mm. The anterior limit of the tunnel was 1–2 mm in the clear cornea making a total width of tunnel from 2.5 to 3.5 mm depending on the desired length of tunnel keeping the length to breadth ratio of 2:1. The tunnel was extended for SICS with 5.5 mm blade to the desired length based on the nucleus size and phaco was performed without extension. Care was taken while extending the tunnel, the extension blade was positioned straight in the stab and globe should be stabilized, so that external incision does not tear away. The length of the self-sealing incision varied from 6 to 6.5 mm for cortical cataract and could be extended safely from 7 to 8 mm for brown and hard Grade IV cataract [Figure 3].
Figure 3: (a) Group A1: Right temporal posterior limbal tunnel in small incision cataract surgery, (b) Group A2: Left nasal posterior limbal tunnel in small incision cataract surgery, (c) Group B1: Right temporal posterior limbal tunnel in phacoemulsification, (d) Group B2: Right nasal posterior limbal tunnel in phacoemulsification

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In phacoemulsification, the surgery was performed with the same approach but a 2.8 mm posterior limbal stab incision was made in right upper temporal position in right eye and upper nasal position in left eye. Phacoemulsification was done by the divide and conquer method. Rest of the steps were same in both the approaches.


   Results Top


Number of males were 66 (66%) and 45 (45%) in MSICS and phacoemulsification groups, respectively, and number of females in MSICS and phacoemulsification groups were 34 (34%) and 55 (55%), respectively (P = 1, not statistically significant (NSS)). The mean age was 57.58 years in MSICS group and 55.8 years in phacoemulsification group. Most of the patients were from rural area, i.e., 84 (84%) in MSICS group and 57 (57%) in phacoemulsification group. More than half of the patients were blind (VA < 6/60) in the eye to be operated, i.e., 77% and 83% in MSICS and phacoemulsification groups, respectively. The pre- and post-operative keratometery is shown in [Table 1] and [Table 2].
Table 1: Preoperative keratometry

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Table 2: Postoperative keratometry

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Mean surgically induced astigmatism was measured by auto refractometer at 6 weeks, which was <1 D in 86% cases in both the groups (+0.62D ± 0.34 in Group A in 83% and +0.46 D ± 0.39 in Group B in 89%). However, the induced astigmatism was further less in phaco group because of smaller incision and this difference was statistically significant (P < 0.001) [Table 3].
Table 3: Distribution of surgically induced astigmatism at 6 weeks in both groups

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The postoperative cylindrical axis was neutral in 2% cases in SICS and 6% in phaco. It was against the rule in 87% in Group A and 67% in Group B. It was with the rule (WTR) in 11% in Group A and 27% in Group B. The difference between the two groups was statistically significant P < 0.0001 [Table 4].
Table 4: Distribution of postoperative refractive axis among the four groups

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Posterior capsular rent was seen in 1% of cases in SICS group and 7% in phaco group. Subconjunctival hemorrhage was the common postoperative finding in SICS group 16% of the cases and 5% in phaco. Striate keratopathy (SK) was common complication in 21% in phaco group and it was 13% in SICS group. The mild hyphema was seen in 2% cases in SICS and 1% in phaco (difference between the two groups SS). Polycystic ovarian was seen in 12% of the cases in SICS and 5% in phaco. All complications were managed appropriately.

The percentage of patients attaining 6/18 or better vision on day 1 postoperatively or at the time of discharge was more in Group A than in Group B (99% vs. 84%). This means that visual rehabilitation is earlier in SICS Group A because many patients in Group B had SK because of the hard cataract, rigid pupil, and more surgical duration. BCVA at 12 weeks was 6/6 and 6/9 in 86% of the patients in Group A and 97% of patients in Group B [Figure 1].

Five surgical steps (Tunnel making, capsulorhexis, nucleus delivery, cortical wash, and IOL implantation) were taken under consideration for grading the surgeon comfort.

Grading was done as:

  • C1: Comfortable - 1 mark was given
  • C2: Convenient - 2 marks were given
  • C3: Difficult - 3 marks were given.


Surgeon comfort in Group A was C1 in 100%, 86%, and 86% in Stage 1, 2, and 3, respectively. It was C2 in 14% of the cases in Stage 2 and 3. In Group B, it was C1 in 100%, 89%, 87% in Stage 1, 2, and 3, respectively. It was C2 in 7% in Stage 2 and 3 and C3 in 3%, 6% in Stage 2 and 3, respectively. The difference in surgeon comfort grading between the two groups was statistically significant (P < 0.001). Patient's symptomatology was accessed by the pain felt by the patient at the first postoperative day through the different approaches as mentioned and was graded as follows:

  • P1: No pain felt by the patient
  • P2: Mild to moderate pain
  • P3: Severe pain felt by the patient.


At the end of surgery, surgical steps were evaluated statistically.

Patient comfort was P1 in both groups.

Mean surgical duration was 30.32 ± 2.81 s, 293.14 ± 62.71 s, and 366.63 ± 39.08 s in Stage 1, 2, and 3, respectively, in Group A and 30.39 ± 2.87 s, 409 ± 36.9 s, and 353.16 ± 49.27 s in Stage 1, 2, and 3, respectively, in Group B. Mean surgical duration was 690.09 s in SICS and 792.29 s in phacoemulsification. The difference between the 2 groups in Stage 2 was statistically significant (P < 0.001).


   Discussion Top


Cataract is not only the leading cause of blindness in the world but it is also an important cause of low vision in both developed and developing countries. The trend in cataract surgery is now toward correction of low vision and any existing refractive error. Even where surgical services are available, low vision associated with cataracts may still be prevalent, as a result of long waiting for operations, cost and lack of information, and transportation problems.

The techniques of cataract surgery have been continuously evolving since its first description by Indian surgeon, Sushruta (6th century BC), who described it in his work the Sushruta Samhita.[4] SICS is the simple, effective, cheap alternative procedure for management of cataract in the developing world.

MSCIS was developed mainly as a cost-effective alternative to phacoemulsification cataract surgery and will be the standard procedure where phaco surgery is not possible.[1] In the developing countries where the cost is a major issue and number of surgeries performed by a surgeon is large, duration of surgery is not only important for handling more patients but also there is lesser tissue handling, coaxial light exposure, and less disturbances to ocular physiology [Figure 4].
Figure 4: Postoperative photograph of a patient with phaco surgery at 6 weeks

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Maximum number of the patients in our study had preoperative VA <6/60. This might be due to the fact that most of our catering population is from rural setup, which seeks medical attention only when they become visually handicapped.

The difference between intraoperative complications was not statistically significant. Subconjunctival hemorrhage was the most common (16%) postoperative finding in SICS group and 5% in phaco group. The subconjunctival bleeding was due to the posteriorly located incision, where conjunctival vessels are present and cautery was not used. The SK was the most common (21%) complication in phaco group and it was seen in 7% of SICS group. Posterior capsular rent was seen in 1% of cases in SICS group and 7% in phaco group. SK and posterior capsular rent was higher in phaco group due to higher use of energy and manipulation in harder cataract (advanced Immature senile cataract or mature senile cataract). As most patients in our setup opt for late surgery once they have significant visual loss (<6/60). Hyphema was seen in 2% cases in SICS and 1% in phacoemulsification (statistically significant, P = 0.0001) but did not require surgical intervention. It was because of the posteriorly located incision where the conjuctival vessels are patent and the larger size of the incision in SICS. None of the patient in the two groups with oblique limbal stab incision had leaking anterior chamber or endophthalmitis.

The amplitude of postoperative astigmatism was higher in Group A (1.16 + 0.37) than in Group B (0.88 + 0.57). The difference between the two groups was statistically significant P < 0.001. Pipat Kongsap documented[5] that a superior scleral incision was associated with slight against-the-rule astigmatism (flatter vertical axis), while a temporal scleral incision was associated with slight with-the-rule astigmatism (flatter horizontal axis). Our study differ from the previous studies in respect to against the rule as major postoperative axis, possibly due to the temporal incision taken in these studies as compared to oblique incision taken in our study.

The site superotemporal (right eye) or superonasal (left eye) incision provides more space on the sides than superiorly in the absence of superior rectus suture. Planes of incision and intraocular manipulations are more accurate as eye is straight with better fundal glow rather than in down gaze position, as occur in superior rectus suture. The tunnel is created as one-step incision and 2nd step during extension; so the opposing surfaces are smoother for better sealing and healing. The closure placement of the tunnel to the limbus also facilitates delivery of nucleus.

Mean surgically induced astigmatism in Group A was 0.63 ± 0.34 D and 0.45 ± 0.39 D in Group B which was statistically significant (P = 0.001 which is statistically significant). Oblique limbal stab incision in phaco causes less astigmatism. A 2.8 mm incision is too small to alter the corneal shape. Such an incision maintains the preoperative cylinder profile. Large incisions cause more flattening. The site of incision is between the horizontal and vertical meridian, which is the reason for lesser astigmatism in both the techniques (<1 D). We did not use cauterization in this technique which too reduced scaring and hence astigmatism. The surgically induced astigmatism with this technique is comparable with standard scleral incision cataract surgery but is more as compared to phaco. When the incision is located superiorly, both gravity and eyelid blink tend to create a drag on the incision. The superotemporal incision has a better wound strength due to minimal seperational force of the lid pressure and gravity.[6]

Total time taken for surgery during Group A 690.09 s as compared to 409 s in Group B. More time was taken in phacoemulsification group because most of the cases were having hard nucleus and hence surgeon comfort was also less. The technique of direct limbal stab incision reduces the overall surgical time to 9–12 min by eliminating five surgical steps and related complications - superior rectus stitch, conjunctival flap, cautery, incision, and tunnel making. Thus, the difference in surgical duration between the two groups was statistically significant (P < 0.001). The lesser duration of surgery is very important because it reduces tissue manipulation and is useful in high volume surgery.

With the use of this technique, overall surgical time is reduced to 5–8 min by eliminating three surgical steps - superior rectus stitch, conjunctival flap, and cautery. There are also no chances of postoperative ptosis as superior rectus suture is not applied. The healing of incision is also very fast as conjunctival vessels are patent and epithelialization covers the clean incision site quickly, good comfort, and visual outcome.

Patient's comfort is related to anesthesia during surgery and pain during postoperative period, which in turn is dependent on the tissue manipulation and extent of tissue damage caused by a procedure. Patient comfort was P1 in both the groups because with this technique we least disturbed the ocular physiology.

At 12 weeks 26% patients in Group A and 83% patients in Group B had VA 6/6. During whole course, postoperative VA remained statistically insignificant between two groups (P > 0.67) [Table 5]. Ashwini et al. in their Hyderabad study reported that 82% of the patients in temporal group had VA of >6/9 compared to superior group in which only 78% of the patients had VA of better than 6/9. Results are consistent with our study.[7]
Table 5: Distribution of visual acuity in 4 groups at 12 weeks

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Ruit et al.[8] compared the efficacy and visual results of phacoemulsification versus SICS for the treatment of cataracts. At 6 months, 89% of the SICS patients had uncorrected VA (UCVA) of 20/60 or better and 98% had a best-corrected VA (BCVA) of 20/60 or better versus 85% of patients with UCVA of 20/60 or better and 98% of patients with BCVA of 20/60 or better at 6 months in the phaco group (P = 0.30). Surgical time for SICS was much shorter than that for phacoemulsification (P < 0. 001). They concluded that SICS is a more appropriate surgical procedure for the treatment of advanced cataracts in the developing world.

Gogate et al.[9] compared the efficacy, safety, and astigmatic change after cataract surgery by phacoemulsification and MSICS. They found that 68.2% patients in the phacoemulsification group and 61.25% patients in the SICS group had UCVA better than or equal to 6/18 at 1 week. At 6-week follow-up, 81.08% patients in the phacoemulsification group and 71.1% patients in the SICS group had UCVA of better than or equal to 6/18. They concluded that both phacoemulsification and SICS are safe and effective for visual rehabilitation of cataract patients although phacoemulsification gives better UCVA in a larger proportion of patients at 6 weeks.

Reddy et al.[10] compared the astigmatism induced by superior and temporal incisions in MSICS and compared the astigmatism induced by clear corneal incision versus scleral tunnel in phacoemulsification surgery. A total of 64 eyes of 64 patients (34 male/30 female) with a mean age of 62.10 years (range: 45–82 years) were included in the study. They found a significant against the rule shift in astigmatism in the phacoemulsification group and the MSICS superior incision group. The MSICS group with temporal incision had with-the-rule shift in astigmatism. At 90 days, conventional SICS superior incisions showed 1.92 ± 0.53 D of against the rule astigmatism and temporal incisions showed 1.57 ± 0.24 D of WTR astigmatism. Phacoemulsification with clear corneal incisions and scleral pocket showed 1.08 ± 0.36 D and 1.23 ± 0.71 D of astigmatism, respectively.

Thus, astigmatism with this technique is significantly less as compared to SICS and phacoemulsification done by clear corneal approach. Mean surgically induced astigmatism in Group A was 0.63 ± 0.34 D and 0.45 ± 0.39 D in Group B (P = 0.0015 which is statistically significant). The clear corneal incision has advantages like shorter tunnel length, no need of cauterization but it causes more astigmatism, infections and requires suturing if length of incision is larger than 3.2 mm. Hence it is not suitable for SICS. Hence, a direct posterior limbal incision has the advantages of both and the surgery is faster, has easier AC approach, lesser astigmatism, and rigid IOL can be implanted without suture.


   Conclusion Top


One can eliminate the steps of bridle stitch, conjunctival flap, and cauterization and self-sealing tunnel can be made in single step by keratome 2.8 mm as done for phaco but at the posterior limbus and extended in second step for SICS. The technique is as effective, easy, less time-consuming, and eliminate the complications of these additional steps. SICS with oblique limbal stab incision technique is a rapid, cost effective and good alternative to phacoemulsification in hilly areas since the final visual outcome is the same with both the techniques. Although duration was more with phacoemulsification, it was because of the learning curve of phacoemulsification and the surgeon was an experienced SICS surgeon. The fact that the patients with rigid pupil and pseudoexfoliation were more in Group B also increased the duration in Group B. Surgically induced astigmatism was less with phacoemulsification (less than one diopter), with the advantage of extension without suturing, in cases where required (rigid intraocular lens and complicated cases). Phacoemulsification gives better BCVA in a larger proportion of patients at 12 weeks, so it is a good option with controlled parameters.

What was known?

Standard MSICS is done by constructing a self-sealing tunnel using four different knives (incision blade, crescent knife, keratome, and extension blade) after bridle stitch, conjunctival flap, and cauterization, which consume more time, requires multiple steps. Conventional SICS superior incisions showed 1.92 ± 0.53 D of against the rule astigmatism and temporal incisions showed 1.57 ± 0.24 D of WTR astigmatism. Phacoemulsification with clear corneal incisions and scleral pocket showed 1.08 ± 0.36 D and 1.23 ± 0.71 D of astigmatism, respectively.

What this paper adds

One can eliminate the steps of bridle stitch, conjunctival flap, and cauterisation and self-sealing tunnel can be made in single step by keratome 2.8 mm as done for phaco but at the posterior limbus and extended in second step. The technique is as effective, easy, less time-consuming and eliminate the complications of these additional steps. Astigmatism introduced by this technique in phaco is less than the clear corneal and scleral incisions in phacoemulsification. Surgically induced astigmatism was less with phacoemulsification (less than one diopter), with the advantage of extension without suturing in cases where required (rigid intraocular lens and complicated cases).

Acknowledgment

I would like to thank the entire ophthalmology department which worked as a team for doing various procedures for the patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Sharma RL, Panwar P. Minimal Duration Cataract Surgery (MDCS)-Small incision cataract surgery (SICS) without superior rectus stitch, no conjunctival flap and no cauterization. Delhi J Ophthalmol 2012;22:275-8.  Back to cited text no. 1
    
2.
Ernest P, Tipperman R, Eagle R, Kardasis C, Lavery K, Sensoli A, et al. Is there a difference in incision healing based on location? J Cataract Refract Surg 1998;24:482-6.  Back to cited text no. 2
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3.
Colleaux KM, Hamilton WK. Effect of prophylactic antibiotics and incision type on the incidence of endophthalmitis after cataract surgery. Can J Ophthalmol 2000;35:373-8.  Back to cited text no. 3
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4.
Sharma PV. Susruta-Samhita. Vol. II. Varanasi, India: Chaukhambha Visvabharati Oriental Publishers & Distributors; 2001.  Back to cited text no. 4
    
5.
Kongsap P. Visual outcome of manual small-incision cataract surgery: Comparison of modified Blumenthal and Ruit techniques. Int J Ophthalmol 2011;4:62-5.  Back to cited text no. 5
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6.
Gokhale NS, Sawhney S. Reduction in astigmatism in manual small incision cataract surgery through change of incision site. Indian J Ophthalmol 2005;53:201-3.  Back to cited text no. 6
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7.
Ashwini KV, Gupta CN, Sandhya R. Effect of incision location on post-operative astigmatism in manual small incision cataract surgery. Chakshu 2011;28:56-9.  Back to cited text no. 7
    
8.
Ruit S, Tabin G, Chang D, Bajracharya L, Kline DC, Richheimer W, et al. A prospective randomized clinical trial of phacoemulsification vs. manual sutureless small-incision extracapsular cataract surgery in Nepal. Am J Ophthalmol 2007;143:32-8.  Back to cited text no. 8
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9.
Gogate PM, Kulkarni SR, Krishnaiah S, Deshpande RD, Joshi SA, Palimkar A, et al. Safety and efficacy of phacoemulsification compared with manual small-incision cataract surgery by a randomized controlled clinical trial: Six-week results. Ophthalmology 2005;112:869-74.  Back to cited text no. 9
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10.
Reddy B, Raj A, Singh VP. Site of incision and corneal astigmatism in conventional SICS versus phacoemulsification. Ann Ophthalmol (Skokie) 2007;39:209-16.  Back to cited text no. 10
[PUBMED]    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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