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 Table of Contents  
Year : 2021  |  Volume : 59  |  Issue : 4  |  Page : 338-343

Minimizing topical medication in cataract surgery

1 Department of Cataract and Cornea, Chandraprabha Eye Hospital, Jorhat, Assam; Department of Ophthalmology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
2 Department of Ophthalmology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
3 Department of Cataract and Cornea, Chandraprabha Eye Hospital, Jorhat, Assam, India

Date of Submission13-May-2021
Date of Acceptance10-Jul-2021
Date of Web Publication21-Dec-2021

Correspondence Address:
Dr. Sandip Sarkar
Department of Ophthalmology, Jawaharlal Institute of Postgraduate Medical Education and Research, Gorimedu - 605 006, Puducherry
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/tjosr.tjosr_61_21

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Cataract surgery requires the use of multiple topical eye drops application in the pre and postoperative period. Certain strategies offer the patient and surgeon assured drug delivery without topical eye drop instillation avoiding the pitfalls of patient drug compliance, incorrect instillation, and topical drop-associated side effects. The aim of the current review is to evaluate the aspects of drop-free cataract surgery starting from intraoperative pupil dilation to intravitreal drug instillation.

Keywords: Dropless cataract surgery, endophthalmitis prophylaxis, iris dilation, topical medication, transzonular

How to cite this article:
Sarkar S, Kasturi N, Bardoloi N. Minimizing topical medication in cataract surgery. TNOA J Ophthalmic Sci Res 2021;59:338-43

How to cite this URL:
Sarkar S, Kasturi N, Bardoloi N. Minimizing topical medication in cataract surgery. TNOA J Ophthalmic Sci Res [serial online] 2021 [cited 2022 Dec 10];59:338-43. Available from: https://www.tnoajosr.com/text.asp?2021/59/4/338/333176

  Introduction Top

Phacoemulsification is one of the most commonly performed elective surgical procedures worldwide.[1] The improved surgical methods and newer instruments have significantly reduced the surgical complications, and have been able to increase the expectation level of a successful visual outcome.[2],[3] The existing pattern of practice in modern phacoemulsification includes preoperative use of antibiotics for endophthalmitis prophylaxis, mydriatic eye drops for iris dilation, prophylactic use of postoperative antibiotics, and anti-inflammatory eye drops to control the inflammation following cataract surgery.[4] Topical eye drop instillation may have some disadvantages such as patient compliance, cost, and adverse effects on the environment from single-use, plastic bottles.[5]

In earlier days, an injectable steroid was given to control the postoperative inflammation.[6],[7] Antibiotics were mixed with irrigating solutions to prevent endophthalmitis.[8] However, these regimens could not gain much popularity due to the absence of safety and efficacy of the products, increased risk of infection, toxic anterior segment syndrome, or concentration error from the available products.[9]

Currently, modern phacoemulsification surgery is a daycare procedure, providing the earliest rehabilitation to the patients.[10] However, one major disadvantage of cataract surgery is that the patient has to put multiple eye drops into the eye for at least 1 month.[11] There are issues of patient compliance, damage of the ocular surface from the preservatives present in the eye drops, and numerous call-backs. This review will focus on the substitution of eye drops in favor of other modes of drug delivery in major areas of cataract surgery such as pharmacologic pupillary mydriasis, endophthalmitis prophylaxis, inflammation control, and postoperative cystoid macular edema (CME) following cataract surgery.

  Disadvantages of Topical Medication Top

Hermann et al. in their compliance monitoring study showed that patient's compliance toward the number of prescribed eye drops following cataract surgery was quite low.[5] Another study reported noncompliance with eye drops is as high as 40%.[12] Noncompliance with the prescribed medication can easily increase the infection chances and may impose a greater health safety issue. Moreover, nonadherence to the prescribed drug plan for antibiotic eye drops can increase bacterial resistance.[13] Few patients even use a faulty technique for postoperative eye drop instillation.[14] Few examples of faulty techniques for eye drop application include failure to put the drop into the eye, putting higher number of drops in a single dose, polluting the bottle tip, etc.[15] The reported incidence of a faulty technique of eye drops administration can be as high as 93%.[14] Corneal and conjunctival abrasions have also been reported in older people during eye drop application.[16] The possibility of wound dehiscence and ingress of fluid into the anterior chamber (AC) following faulty technique during eye drop application has also been reported.[17] Therefore, it may be to raise the chances of endophthalmitis from the very treatment which is supposed to avert it.

Iris Dilation

For routine cataract surgery, pupil dilation is done by topical instillation of anticholinergic or sympathomimetic agents.[18] However, a very small amount (<1%) of topical mydriatics absorbed through the cornea, therefore a higher concentration of the drug is needed to ensure sufficient pupil dilation during surgery.[19] These topically administered drugs can go systemic absorption through mucosal blood vessels and cause malignant hypertension, acute pulmonary edema, or myocardial infarction in patients with poor cardiac function.[20],[21] However, the presence of preservatives in topical medication such as benzalkonium chloride can lead to corneal toxicity which can hinder the surgeon's view during surgery.[22] In addition, topical mydriatics can produce good pupil dilation in the early stages of surgery, but it can go off as the surgery as surgery proceeds needing additional maneuvers.[23] Meanwhile, intraoperative pupillary constriction is a well-known phenomenon in patients with intraoperative floppy iris syndrome and diabetes mellitus.[24]


According to the American Society of Cataract and Refractive Surgery (ASCRS) survey in 2007, a majority (91%) of the surgeons were using topical antibiotics preferably fluoroquinolones (gatifloxacin or moxifloxacin) preoperatively for endophthalmitis prophylaxis during cataract surgery.[25] However, to date, no evidence is found which proves that perioperative use of antibiotics reduces the postoperative endophthalmitis.[26] Only, topical povidone–iodine applied on the ocular surface during cataract surgery proved to be effective in lowering the chances of endophthalmitis. Due to the poor corneal penetration of the eye drops, only a low-concentration of antibiotic is achieved in the AC.[27] Still, topical fluoroquinolone moxifloxacin was found to have the lowest mean inhibitory concentration for most bacterial organisms causing endophthalmitis.[28]

Prophylactic antibiotics are required for 1–2 weeks duration, only until the wound heals. Application of antibiotic-steroid combination eye drops is futile.


Topical corticosteroids have been acknowledged as the primary weapon to control the postoperative inflammation and pain for years now. Prednisolone acetate is one of the most important drugs in that category due to its longer period of action. Although not as potent as dexamethasone, still works marvelously.[29] There are few studies which emphasize to replace corticosteroids with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), but concrete evidence is still vague. The literature is full of comparative studies on steroids and nonsteroidal anti-inflammatory agents (NSAID). In routine practice, the general belief is that a combined regimen of corticosteroids with NSAID works better than corticosteroid alone in controlling postoperative inflammation.[30] However, no large scale, prospective data is available to support any benefits in adding NSAID to the regimen. Another aspect of phacoemulsification surgery is dry eye,[31],[32] as many patients suffer from dry eye postsurgery and the presence of preservatives in eye drops will increase the severity of dry eye disease.

  Drop-Free Strategy Top

The drop-free approach for cataract surgery involves using intracameral injection of mydriatics for iris dilation, intracameral and intravitreal injection of antibiotics for endophthalmitis prevention, and intravitreal injection of steroids for controlling inflammation and reduction of CME.

  Dilation Top

Intracameral use of mydriatics for intraoperative pupil dilation was first evaluated by Lundberg and Behndig where they compared preoperative mydriatics with intracameral mydriatics for routine phacoemulsification surgery.[33] They found that intracameral use of lidocaine and phenylephrine delivered faster but less pupillary in comparison to topical mydriatics and they did not show any tendency toward intraoperative pupil constriction.

Intraoperative pupillary miosis is a well-known phenomenon in patients with intraoperative floppy iris syndrome (IFIS) after the Food and Drug Administration (FDA) approved tamsulosin for the treatment of benign prostatic hyperplasia. Intracameral use of 1.5% phenylephrine has shown great results in dilating the pupil and stabilizing the iris tone in patients with IFIS.[34] Intracameral phenylephrine has shown comparable results, even with darkly pigmented iris.[19]

Many authors have compared the efficacy of topical mydriatics with intracameral lidocaine 1.0% alone or in combination with other mydriatic drugs such as cyclopentolate 0.1% and phenylephrine 1.5%. The study results showed that the intracameral lidocaine alone was sufficient enough to produce prompt and adequate iris dilation for a comfortable phacoemulsification cataract surgery.[35] Moreover, due to its anesthetic property, it enhances the comfort level of the patient during the surgery. Studies showed that bisulfite, the preservative used in epinephrine showed no toxicity toward corneal endothelium.[36]

Sengupta et al. did a prospective study the compare the efficacy of a standardized wick soaked in a mydriatic cocktail regimen (2.5% phenylephrine, 0.5% moxifloxacin, 1%, cyclopentolate, and 0.03% flurbiprofen eye drops) and compare it with the preexisting regimen of topical dilating for preoperative mydriasis in cataract surgery.[37] They showed significant better mydriasis in the cocktail group in comparison to the control group. Similar studies using standardized wick with mydriatic cocktail also showed better results than the preoperative topical mydriasis group.[38] Many authors have used adrenaline in irrigating solution for maintenance of mydriasis during cataract surgery with significantly favorable results. Corbett and Richards did a prospective, randomized double-blind study to evaluate the safety and efficacy of intraoperative adrenaline in irrigating solution for pupil dilation during cataract extraction and it showed significantly higher iris dilation than preoperative regimen at 20 min (P < 0.001) and 30 min (P < 0.01) into the surgery.[39]

Mydrane, a commercially available mydriatic used for intracameral use contains a combination of tropicamide, phenylephrine, and lidocaine. In a comparative study by Chiambaretta F et al B and associates, mydrane was compared with topical mydriatics in routine cataract surgery and the results showed quicker maximal pupil dilation, better theater turnaround, and higher patient satisfaction.[40]

The drug OMS302 (Omidria [contains phenylephrine 1% and ketorolac 0.3%]) is approved by the USA FDA for intraoperative mydriasis and postoperative ocular discomfort. The drug was mixed with the routine irrigating solution during phacoemulsification for intraoperative iris dilation and postoperative ocular pain. This drug proved to be better than a single injection of intracameral epinephrine for decreasing postoperative pain, surgical time, and the need for pupillary dilation manoeuvres.[41]

  Endophthalmitis Prevention Top

The intracameral antibiotics have become the go-to approach for endophthalmitis prophylaxis due to the effectiveness and safety margin toward the cornea and retina.


The most important advantage of intracameral antibiotic injection is the capacity to deliver high-concentrated antibiotics into the operated site. Montan et al. did the first large-scale study to evaluate the efficacy of intracameral cefuroxime to prevent the postoperative endophthalmitis and the results were quite encouraging.[42] After that, the European Society of Cataract and Refractive Surgeons (ESCRSs) conducted a large scale, prospective, multicentred, and randomized controlled study to evaluate the advantages of intracameral cefuroxime injection in the prevention of postoperative endophthalmitis.[43] The ESCRS study showed a 5-fold reduction in the postoperative endophthalmitis rates after the usage of intracameral injection of cefuroxime. This study was conducted all over Europe and the results were so astonishing, but it had to be stopped midway to provide the same advantage to the control group and the committee found a clear advantage of using it. A recently conducted study by Haripriya et al.[44] in India showed the effectiveness of intracameral moxifloxacin as a prophylactic agent for postoperative endophthalmitis. The study being the largest till date regarding intracameral use of antibiotics showed that it can statistically reduce the rate of infection. The All India Ophthalmological Society member online survey of prophylactic antibiotic practice patterns showed that a majority of the Indian surgeons are currently using intracameral antibiotics in routine cataract surgery.[45] Further studies also supported the efficacy of both cefuroxime and moxifloxacin injection in preventing postcataract endophthalmitis.[46],[47] The use of intracameral antibiotics has been widely accepted in countries like India, the USA, Sweden, and the endophthalmitis rates in these parts of the world are astoundingly low (1 in 5000 cases). From the days of clear corneal incision when endophthalmitis rate was 1 in 400 cases, this is an extremely encouraging result.[48]


The choice of prophylactic antibiotic is based on the analysis of the prevalence of endophthalmitis-causing organisms in the locality of the operating center and where the patient lives. Cataract surgeons across Europe have an approved, commercially available drug cefuroxime for intracameral use. They had a satisfactory outcome with cefuroxime in reducing postoperative endophthalmitis. The overall incidence has substantially dropped down, until encountered cefuroxime-resistant enterococcus endophthalmitis patients.[49] In India, a majority of the postoperative endophthalmitis cases are caused by gram-negative organisms, that's why intracameral injection of moxifloxacin is found to be superior to cefuroxime.[44],[47] Moreover, in India, surgeons have a commercially available economical drug moxifloxacin, so practice adoption was not that difficult. In the United States, though no FDA-approved drug is available for intracameral use, still moxifloxacin is the most preferred option. This may provide a theoretical advantage against the gram-negative organism, but the gram-positive organism which is a major cause of endophthalmitis in the United States, still a concern.[50]

Vancomycin was the most preferred option against the gram-positive organism once upon a time, but due to the risk of hemorrhagic occlusive retinal vasculitis, it has gone out of favor.[51] Srinivasan et al. did a prospective randomized study to evaluate the efficacy of adding vancomycin in irrigating solutions, in comparison to topical ciprofloxacin given preoperatively for a day, during phacoemulsification, in reducing the AC contamination. The aqueous samples obtained at the end of surgery showed significantly ([P = 0.001]) lesser amount microbial growth in the vancomycin group than the preoperative topical antibiotics group.[52] Moreover, the USA government and ASCRS have issued guidelines against the usage of vancomycin as an intracameral antibiotic in routine cataract surgery.


Currently, among the two most commonly used drugs for intracameral use, cefuroxime seems to be safer than moxifloxacin at 1 mg dosage.[53] It is reported to cause macular edema at a dose of 9 mg and permanent corneal, retinal damage at a dose excessive of 50 mg.[54] Intracameral injection of accurate dosage of cefuroxime has been reported to cause subclinical changes in the macula, which have been picked up by optical coherence tomography.[55]

Although moxifloxacin is the most commonly used drug, no established dose or regimen has been developed till date for intracameral usage. Surgeons have tried injection volumes from 0.03 ml (166 mg) to 0.1 ml (500 mg) and “full strength” moxifloxacin (0.5%) for intracameral use.[56] Moxifloxacin has a narrow therapeutic index than cefuroxime as it is toxic to the corneal endothelium toxic at a dose of 500 mg/ml.[57] To overcome this issue, a larger volume of at least 0.4–0.5 ml at a concentration of 0.1% has been advocated.[58]

  Inflammation Suppression Top

Drop-free strategies

Many authors have described the various approaches for drop-free management of postoperative inflammation following cataract surgery. Among them, intracameral injection of antibiotics with subconjunctival injection of steroids is the simplest approach. Along with it, all other newer techniques, technologies have been described below.

Intracameral antibiotic with subconjunctival steroid

Rattan et al. did a prospective randomized study to evaluate the efficacy of intracameral moxifloxacin 0. 1% with subconjunctival injection of steroid (triamcinolone acetonide 4 mg) in comparison with postoperative topical drops as an anti-inflammatory agent following phacoemulsification.[59] In their study, they found similar infection and inflammation rates in both groups. Another prospective study showed reduced macular thickness on optical coherence tomography (OCT) and similar visual outcome with 20 mg injection of subconjunctival triamcinolone acetonide with drops.[60]

Intravitreal injection

Another innovative approach for injecting antibiotics and anti-inflammatory drug is through the trans-zonular route.[61] Dropless cataract surgery is a new technique developed and practiced by few cataract surgeons in the USA.[62],[63] Two specially prepared regimens named Tri-Moxi (containing triamcinolone acetonide and moxifloxacin) and Tri-Moxi-Vanc (vancomycin added to the regimen) are used. After intraocular lens (IOL) implantation, the surgeon administers the drug through a trans-zonular route into the vitreous cavity [Figure 1].[15] This eradicates the requirement of putting the eye drops after the surgery and patients can live their routine life without any obligation. There have been few published studies worldwide regarding technique, with excellent results, and without any significant complication. In India, Bardoloi et al. did a prospective study to evaluate the safety and efficacy of dropless cataract surgery.[15] As commercially formulated Tri-Moxi product was not available in India, so the mixture was prepared on the operation theater from freshly opened vials of moxifloxacin eye drops and triamcinolone acetonide and injected transzonularly. The results of the study were quite satisfactory, majority of the patients achieved uncorrected visual acuity of better than 6/9, none of the patients required any topical medication in the postoperative period. Another important aspect of the study that nobody developed raised intraocular pressure following dropless cataract surgery.
Figure 1: The figure showing the steps of dropless cataract surgery. (a) injection of cohesive ophthalmic viscosurgical device into the ciliary sulcus for creating some space, (b) Placement of 27 gauge cannula in the transzonular space, (c) injecting the mixture and a plume of mixture distinctly visible in the vitreous cavity. (d) Bimanual irrigation and aspiration to remove the remaining ophthalmic viscosurgical device

Click here to view

Another issue with the technique includes the lack of comparative and data regarding safety, efficacy, and long-term risk of damage to the zonular matrix and the retina. A recent case series of four cases of postoperative endophthalmitis has been reported which raising further concern regarding this technique.[64]

Newer developments

The USA FDA in 2018 approved a newer agent Dexycu (Eyepoint Pharmaceuticals, Watertown, USA) for postoperative management of AC inflammation. Following the conclusion of phacoemulsification, the surgeon injected the IBI-10090 suspension of dexamethasone as a single 5-ml droplet through the intracameral route into the AC with a 30-gauge needle. The new agent has shown a more favorable outcome than placebo therapy for reducing of AC reaction.[65] In another study, IBI-10090 AC intracameral dexamethasone drug-delivery suspension (Dexycu) was compared with prednisolone acetate eye drops for treating AC inflammation following cataract surgery. The results were comparable and the patients liked the drop-free approach more, but it was associated with raised intraocular pressure.[66]

Recently, the USA FDA has approved dexamethasone impregnated canalicular plug (Dextenza, Ocular Therapeutix, Bedford, USA) and the Phase III trials are showing better results than placebo in postoperative control of the AC inflammation.[67] Recently, an IOLs presoaked in antibiotics and NSAID is in the developing phase, which may provide a higher concentration of drug in the early postoperative period.[68]

  Conclusion Top

Drop-free approaches provide the patient and surgeon guaranteed drug delivery and prevent the pitfalls of patient adherence, improper drug application, and topical drug-related corneal issues. The literature search showed that these strategies of drop-free cataract surgery are advantageous, efficacious, and safe. The “dropless cataract surgery” can be a major boon to the working rural population in countries like India where putting 3–4 eye drops 3–4 times is not just cumbersome but unsafe as well.

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Conflicts of interest

There are no conflicts of interest.

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