The Rationale Behind Using Medical Regimens for Cataract Surgery

Cataract surgery has been shown to have a positive impact on mental health, leading to improved vision-related quality of life in elderly patients as well as improvements in cognitive function and depressive mental status.^1,2 This improvement in quality of life is rapid after surgery. Consequently, it is imperative that cataract surgeons do everything possible to maximize visual outcomes in these patients in the immediate postoperative period. This involves reducing the risk of infection and inflammation through meticulous, efficient surgical technique and appropriate treatment regimens pre- and postoperatively. There are a number of pearls cataract surgeons should keep in mind when managing cataract patients (Table 1).³

Reducing Ocular Infection Risk Following Cataract Surgery

The incidence of endophthalmitis following cataract surgery varies and depends on a multitude of factors. There is a higher incidence associated with clear corneal incisions (0.043%) compared to scleral incisions (0.049%).⁴ This higher incidence should be taken into consideration when these types of incisions are created. The experience of the surgeon has also been shown to affect the incidence of endophthalmitis. In a study at Aravind Eye Hospital in Pondicherry, India, the rate of endophthalmitis among full-time staff was 0.02% compared to 0.33% among surgeons in training.⁵

In a study examining the 10-year incidence of acute-onset endophthalmitis after cataract surgery, the rate of endophthalmitis was observed to be 0.085% for clear corneal phacoemulsification. The incidence of endophthalmitis was 0.053% during the first 5 years of the study and 0.08% during the last 5 years. Upon investigation of the culture isolates, it was found that 35% of infections were due to Staphylococcus species, 35% were due to Streptococcus species, 15% were polymicrobial, and 5% were due to Propionibacterium acnes.⁶

Newer-generation fluoroquinolones, such as besifloxacin, gatifloxacin, and moxifloxacin, are effective in reducing the incidence of endophthalmitis. A study in Utah examined more than 20 000 cataract cases managed postoperatively with newer-generation fluoroquinolones to determine whether they had an effect on the rate of endophthalmitis.⁷ Results demonstrated that 14 patients developed endophthalmitis, an overall rate of 0.07%. Six cases occurred after the drops were stopped at 7 days. All but 1 case occurred within 9 days of surgery. The 1 case that did not occur within 9 days occurred at 22 days and was most likely due to a leaking wound. A lower but not significant incidence of endophthalmitis was observed with the use of gatifloxacin compared to moxifloxacin (0.06% vs 0.13%, P=.11).⁷ In terms of the endophthalmitis cases that presented while antibiotics were still being administered, the rate of occurrence with gatifloxacin was 0.025%, and the rate of occurrence with moxifloxacin was 0.105%.⁷

Implementation of antibiotics perioperatively in addition to postoperatively may be important for reducing the incidence of endophthalmitis. The European Society of Cataract & Refractive Surgeons (ESCRS) conducted a study investigating the effects of prophylaxis for postoperative endophthalmitis following cataract surgery.⁸ Patients enrolled in this study were divided into 4 groups. One group did not receive perioperative antibiotics; another group received an intracameral injection of cefuroxime; a third group was administered topical levofloxacin only; a fourth group was administered an intracameral injection as well as topical levofloxacin. Results indicated that the incidence of endophthalmitis was lowest in patients receiving the combination of treatments. The incidence rate was 0.05% in this group, compared to 0.251% in the group receiving topical levofloxacin treatment only, 0.075% in the group receiving intracameral cefuroxime treatment only, and 0.326% in the group receiving no perioperative prophylaxis.⁸ These results indicate that intracameral injections of cefuroxime are effective in reducing the incidence of endophthalmitis, and they are even more effective when used in combination with topical levofloxacin.

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The ESCRS endophthalmitis study concluded that the absence of an intracameral cefuroxime prophylactic regimen (1 mg in 0.1 mL BSS) increased the risk of endophthalmitis 4.92-fold.⁸ This study also found that, compared to scleral tunnels, the risk of endophthalmitis was increased 5.88-fold with clear corneal incisions. Silicone IOL optic material was associated with a 3.13-fold increased risk compared to acrylic. Moreover, the presence of surgical complications was associated with a 4.95-fold increased risk of endophthalmitis. The risk was also increased if less experienced surgeons were performing the procedure.⁸

Prophylaxis with antibiotics

These studies indicate that prophylaxis with antibiotics is critical for reducing the risk of infection. The combination of intracameral antibiotics, such as vancomycin 20 µg/mL, and topical fluoroquinolones, such as gatifloxacin, moxifloxacin, or besifloxacin, is effective in reducing the incidence of endophthalmitis.

The results from the study in Utah indicated that when newer-generation fluoroquinolones were administered postoperatively for 7 days, a peak incidence of endophthalmitis occurred after 9.3 days.⁷ This suggests that the use of antibiotics should be extended in the prophylaxis of endophthalmitis following cataract surgery. Fluoroquinolone treatment should be initiated 3 days prior to surgery and continued for 2 weeks following surgery. Ensuring that wounds are competent before stopping antibiotic treatment is critical in reducing the risk of endophthalmitis.

Wound architecture

The quality of the incision is critical in the reduction of endophthalmitis rates following cataract surgery. If the incision is not water-tight, the surgeon should place 1 to 3 stitches to close the incision. However, surgeons should not assume stitches completely protect against the risk of infection. The architecture of the wound is also critical; the incision is more likely to self-seal the more square it is.

Proper draping

The proper draping of eyelids and eyelashes is important for reducing the risk of infection during surgery. The eyelids and eyelashes must be isolated and out of the surgical field. Proper eyelid and eyelash draping isolates the meibomian gland orifices, reduces exposure of the ocular surface to inflammatory glandular secretions, and improves visualization.

Povidone-iodine solution

Povidone-iodine solution applied immediately before the surgery is effective in reducing the number of organisms residing on the ocular surface at the time of the incision.⁹

Preventing Postoperative Inflammation

The reduction of postoperative inflammation is also critical for improving visual outcomes following cataract surgery. There are pearls for achieving this as well.

Cystoid macular edema prophylaxis

For cystoid macular edema (CME) prophylaxis, the combination of steroids, such as prednisolone, difluprednate, and loteprednol, and nonsteroidal anti-inflammatory drugs (NSAIDs), such as ketorolac, nepafenac, bromfenac, and diclofenac, is beneficial. Studies have shown there is statistically less CME macular thickening <10 microns, and less optical coherence tomography (OCT) evidence of CME in patients treated with a combination of an NSAID and a corticosteroid vs corticosteroid alone.¹⁰ This is a significant finding, as retinal thickening <10 microns results in loss of contrast sensitivity. This is a critical issue with the implantation of premium IOLs, as these patients have high expectations for postoperative visual outcomes and do not want to lose any contrast sensitivity.

For routine cases, therapy should be initiated 3 days before surgery and continued for 4 to 6 weeks after surgery. For high-risk cases, therapy should be initiated 1 week prior to surgery, continued for 4 to 6 weeks or longer postoperatively, and visual acuity should be monitored and OCT evaluation should be performed regularly.

OCT analysis

OCT may detect CME/retinal thickening that is not clinically apparent. OCT analysis is also useful for detecting epiretinal membranes. In studies of more than 1000 patients, there was a 9% incidence of epiretinal membranes that were missed on slit lamp examinations and detected by OCT evaluation (Solomon KD, unpublished data).

The presence of an epiretinal membrane increases the risk of CME and therefore affects the decision-making for a patient desiring premium multifocal IOLs. The patient should be referred to a retina specialist who can decide whether or not it is reasonable to proceed with the surgery. If surgery is appropriate, the presence of an epiretinal membrane also affects the treatment regimen. Typically, patients are treated with fluoroquinolones and NSAIDs 3 days prior to surgery. ^11,12 However, if an epiretinal membrane is present, a steroid should be added to the preoperative treatment regimen to further minimize the breakdown of the blood-aqueous barrier at the time of surgery. ¹³

Future Strategies for Improving Visual Outcomes: Reducing Corneal Edema

Corneal thickening could also have an effect on earlier visual outcomes. High-dose pulse steroids are used to reduce cerebral edema. The corneal endothelium is neuroectoderm in origin, thus there is the potential for pulse steroids to have an effect on corneal endothelial pump function. In a preliminary study, patients were pulsed with difluprednate 0.05%. Significantly less edema was observed on postoperative day 1 relative to prednisolone acetate or control (Solomon KD, unpublished data). Improving visual outcomes at day 1 will significantly increase patient satisfaction, as patients desire visual improvement as early as possible. Thus high-dose pulse steroids exhibit potential for improving edema and outcomes in cataract patients. A multi-center study to further investigate the usefulness of high-dose pulse steroids is underway.

Summary

In summary, meticulous, efficient surgical technique and appropriate treatment regimens pre- and postoperatively can reduce the risks of infection and inflammation. Treatment regimens include intracameral antibiotics, topical fluoroquinolones, steroids, and NSAIDs. Monitoring the retina through OCT analysis before and after surgery is helpful in the detection of possible CME or epiretinal membranes, which would affect visual outcomes. These steps can lead to improved visual outcomes among cataract surgery patients.

References

1. Chandrasekaran S, Wang JJ, Rochtchina E, Mitchell P. Change in health-related quality of life after cataract surgery in a population-based sample. Eye. 2008;22:479–484.
2. Ishii K, Kabata T, Oshika T. The impact of cataract surgery on cognitive impairment and depressive mental status in elderly patients. Am J Ophthalmol. 2008;146:404–409.
3. American Academy of Ophthalmology. Preferred Practice Pattern. Cataract in the Adult Eye. Available at: http://one.aao.org/CE/Practice Guidlines/PPP.aspx. Accessed May 3, 2010.
4. Cooper BA, Holekamp NM, Bohigian G, Thompson PA. Case-control study of endophthalmitis after cataract surgery comparing scleral tunnel and clear corneal wounds. Am J Ophthalmol. 2003;136:300–305.
5. Ravindran RD, Venkatesh R, Chang DF, Sengupta S, Gyatsho J, Talwar B. Incidence of post-cataract endophthalmitis at Aravind Eye Hospital: outcomes of more than 42,000 consecutive cases using standardized sterilization and prophylaxis protocols. J Cataract Refract Surg. 2009;35:629–636.
6. Al-Mezaine HS, Kangave D, Al-Assiri A, Al-Rajhi AA. Acute-onset nosocomial endophthalmitis after cataract surgery: incidence, clinical features, causative organisms, and visual outcomes. J Cataract Refract Surg. 2009;35:643–649.
7. Moshirfar M, Feiz V, Vitale AT, Wegelin JA, Basavanthappa S, Wolsey DH. Endophthalmitis after uncomplicated cataract surgery with the use of fourth-generation fluoroquinolones: a retrospective observational case series. Ophthalmology. 2007;114:686–691.
8. Endophthalmitis Study Group, European Society of Cataract & Refractive Surgeons. Prophylaxis of postoperative endophthalmitis following cataract surgery: results of the ESCRS multicenter study and identification of risk factors. J Cataract Refract Surg. 2007;33:978–988.
9. Speaker MG, Menikoff JA. Prophylaxis of endophthalmitis with topical povidone-iodine. Ophthalmology. 1991;98:1769–1775.
10. Wittpenn JR, Silverstein S, Heier J, et al. A randomized, masked comparison of topical ketorolac 0.4% plus steroid vs steroid alone in low-risk cataract surgery patients. Am J Ophthalmol. 2008;146:554–560.
11. Donnenfeld ED, Perry HD, Wittpenn JR, Solomon R, Nattis A, Chou T. Preoperative ketorolac tromethamine 0.4% in phacoemulsification outcomes: pharmacokinetic-response curve. J Cataract Refract Surg. 2006;32:1474–1482.
12. Solomon R, Donnenfeld ED, Perry HD, et al. Penetration of topically applied gatifloxacin 0.3%, moxifloxacin 0.5%, and ciprofloxacin 0.3% into the aqueous humor. Ophthalmology. 2005;112:466–469.
13. Lee JY, Eun CK, Kim YW, et al. The steroid effect on the blood-ocular barrier change induced by triolein emulsion as seen on contrast-enhanced MR images. Korean J Radiol. 2008;9:205–211.

DISCUSSION

What if a patient is allergic to iodine, or one of the treatments, such as a fluoroquinolone, or an NSAID?

Jay S. Pepose, MD, PhD: If someone tells me they are allergic to something, I ask them what the evidence is for their allergy. If they tell me they experienced anaphylaxis, I would take that very seriously. I may even consider referring them to an allergist to have them tested. If a patient has a true anaphylactic reaction or a history of anaphylaxis with fluoroquinolones, I would consider administering other medications. Potential substitutes are trimethoprim, bacitracin, or other alternatives.

Edward J. Holland, MD: If a patient is allergic to povidone-iodine I use hexachlorophene.

Do you use preoperative antibiotics for routine cataract surgery? If so, which one and when do you start?

Richard L. Lindstrom, MD: I administer 3 doses of moxifloxacin starting one hour prior to surgery. I administer topical and intracameral moxifloxacin at the close of surgery and twice in the recovery room. Then moxifloxacin QID is implemented starting on the day of surgery for 14 days.

Holland: I initiate therapy with moxifloxacin the day of surgery and continue for 7 days, or longer if there is a persistent epithelial problem.

Is vancomycin more effective when in the bottle or when injected in the eye at the end of the case?

Kerry D. Solomon, MD: I believe that when in the bottle, vancomycin does not provide as much protection, because it would not be administered at therapeutic levels.

If endophthalmitis typically occurs at 9 days postoperatively, what is the rationale for the administration of an intracameral injection?

Solomon: An intracameral injection can last 12 to 24 hours. The rationale for its administration is that it may kill organisms present on the surface of the eye that may be introduced into the eye during surgery. An intracameral injection of vancomycin, combined with a competent incision and administration of antibiotics postoperatively, will reduce the risk of infection and improve visual outcomes.

Lindstrom: I use intracameral moxifloxacin and I administer it right out of the bottle. I use a different bottle for each patient, and I send the patient home with that bottle. I inject it into the side port, hydrating the side port, which enhances the seal. A small amount goes into the eye.

However, there is not an absolute way. Some people inject it into the anterior chamber. Moxifloxacin is an effective drug; cefuroxime and vancomycin are also useful.

Why not use oral azithromycin as opposed to topical azithromycin?

Holland: I would rather treat locally than systemically, as there are side effects to systemic medication. There have not been any studies examining oral azithromycin in tissue levels. The effectiveness of topical azithromycin is well established. Topical azithromycin reduces the bacterial count on the surface of the eye and oral azithromycin most likely would not. Because of its properties, azithromycin can penetrate tissue. There are a significant number of patients that respond extremely well to azithromycin that do not respond well to other standard therapies. Azithromycin comes in a gel-like consistency. I have patients apply topical azithromycin like a drop and have them rub any excess gel that spills over into the lid tissue.

Pepose: Being a macrolide antibiotic, azithromycin is effective in the treatment and prevention of blepharitis and in the reduction of inflammation, but it is not effective against methicillin-resistant Staphylococcus aureus (MRSA). Thus azithromycin should not be used as a substitute for prophylaxis; it should be used as an adjunct.

Lindstrom: Azithromycin is helpful to optimize the condition of the ocular surface prior to surgery, but it is not my treatment of choice for surgical prophylaxis.

Solomon: I use fluoroquinolones for all patients undergoing intraocular surgery and refractive surgery.

What is your treatment algorithm for meibomian gland disease in children?

Holland: Children can have significant meibomian gland disease and this condition often goes undiagnosed or misdiagnosed. The treatment is similar to adults except that oral tetracycline agents are not used until the permanent dentition is complete. Warm compresses/lid scrubs and topical azithromycin are my first-line therapies. If there is corneal involvement than topical steroids (loteprednol) are indicated.

Lindstrom: I administer azithromycin QHS for one month and lid hygiene BID. If the disease is severe, I implement a course of loteprednol/tobramycin or dexamethasone/tobramycin QID for 2 weeks and BID for 2 weeks in addition to the azithromycin at bedtime.

Does 50 mg doxycycline lead to increased resistance?

Holland: No, it does not cause resistance and this dose is well tolerated.

Lindstrom: At this dose doxycycline is being used for its anti-inflammatory effect and impact on meibomian quality.

When do you use fish oil and flaxseed oil? What is the dosing schedule?

Holland: Omega-3 fatty acids are first-line agents in the management of meibomian gland disease. They are also useful in treating aqueous tear deficiency dry eye syndrome.

Lindstrom: I implement 1 to 3 grams daily, depending on severity of disease and tolerance.

How should lissamine green staining be used?

Holland: Lissamine green comes in strips, but it is available in solution as well. I use it to screen patients before putting anything in their eyes. Lissamine green should be used before the Schirmer test is performed and before the eyes are stained with fluorescein. Lissamine green stains abnormal epithelium, as opposed to fluorescein, which stains absent epithelium. If a patient has severe dry eye syndrome, lissamine green will stain the cornea and conjunctiva and fluorescein staining may be negative. Lissamine green staining is a more sensitive test. Having office staff aware of signs of ocular surface disease so that they can notify the physician before implementing any drops is helpful.

How long does lissamine green take for optimal staining?

Lindstrom: One minute or less.

Holland: The staining occurs quickly. The key is to have enough dye to get the staining. The most common mistake is not using enough dye.

Since steroids act before nonsteroidal anti-inflammatory drugs (NSAIDs) in the inflammatory pathway, why not use steroids alone?

Pepose: The effect of steroids is not absolute, and breakthrough inflammation may occur. Furthermore, there is evidence of synergy between the inhibition of cyclooxygenase and the PLA₂ enzymes. Therefore, using the combination of a steroid and an NSAID is reasonable.

Should surgeons begin administering steroids preoperatively, in addition to NSAIDs and antibiotics?

Solomon: Yes. I believe this would provide opportunity to further improve post-operative visual outcomes.

Holland: I agree. Some believe that because cystoid macular edema (CME) is not common, it is not necessary to prevent it, and it should just be treated if it occurs. However, treating CME is very different from preventing CME, and CME may have residual effects on the retina. We should do all we can to make visual outcomes as optimal as possible, and that includes changing what we do when we have evidence to support doing it.

Pepose: The toxicity of these medications is very low, thus it makes sense to pre-treat with them.

Lindstrom: Pre-treatment does not change cost structure either, the medications are just being administered earlier.

Do you prescribe topical NSAIDs to patients with a sensitivity to oral NSAIDs?

Lindstrom: Yes.

Holland: If sensitivity means gastrointestinal upset than yes. If sensitivity means a true allergic reaction than no.