 Inder Paul Singh, MD

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The value of lens alignment technology for toric 

 implantation during cataract surgery is generally understood among cataract surgeons. 

However, a topic that is not as prevalent is how surgeons ensure that a multifocal IOL is centered on the visual axis during

ASCRS 2020: Assessing aberration of monofocal toric IOL with enhanced recovery, alignment



Herein, I will share how I utilize lens alignment technology, not only for toric markings but also to verify the visual axis for multifocal lens implantation. 

This approach has become critical for me to confirm proper placement and help decrease postoperative adverse events.


As cataract surgeons, we try to do our best at controlling variables so that we have more predictability with our outcomes. 

As such, there are many preoperative tools at our disposal, including topography, aberrometry, ray tracing, or various alignment systems. 

However, intraoperatively, only recently have we discovered an efficient way of applying the preoperative data we have collected and using them in the operating room. 

Trifocal IOL a key for premium cataract surgery practice


Aberrometry has also been used intraoperatively, but its benefit is in the lens power and alignment of a toric

; however, assistance with alignment and centering of the multifocal lens over the visual axis has been neglected.

My colleagues and I have a variety of technologies that provide

 calculations, identification of the axis of astigmatism, and even software that locates the apex of the lens, which is thought to be the center of the visual axis but is not always. 

Although we have an incredible amount of preoperative data, in surgery, we often find ourselves still guessing or “eyeballing” the placement of the lens. 

For instance, in the past, we have used the Purkinje reflex of the microscope to align and center the lens, which can be affected by patient gaze. We often centered the lens based on the pupil. 

However, if the pupil is irregular, we may not be placing it in the center of the visual axis, and some patients have a high-angle kappa or chord Mu (average chord mu, 0.2 ± 0.11 mm) where the center of the visual axis is not at the center of the pupil. 

 Performance of trifocal toric IOL highlighted in tests



As a result, patients can have up to 0.5 mm to 0.6 mm of difference between the center of the pupil and the center of the visual axis. 

Furthermore, if a patient has irregular or dilated pupils, it interferes with the ability to judge the location of the center of the visual axis due to the distorted pupil and iris.

What I have found revolutionary about using a biometer with lens alignment technology (IOLMaster 700; Carl Zeiss) and a digital marking system (Callisto eye; Carl Zeiss) is that it allows me to use preoperative data and apply them intraoperatively to help position the lens in an efficient and consistent way.

Lens alignment technology gives me a true understanding of where the visual axis is located using swept-source optical coherence tomography with a cross-sectional B-scan view of the eye, allowing me to visually confirm the foveal pit. 



Presbyopia-correcting IOLs: Expanding, improving last frontier



Now I have an accurate and confirmatory measurement to ensure that my preoperative data actually measure the center of visual axis. 

Of equal importance, the lens alignment technology takes images of the episcleral vessels preoperatively and can be applied to a digital marking system intraoperatively. 

I am able to send the information to the digital marking system using digital software or I can transfer the data using a USB drive. 



Striving for perfection: Creating the perfect IOL



Intraoperatively, the digital marking software will register and align the scope view of vessels with the image taken by the lens alignment technology to ensure proper alignment. 

For toric lenses this is ideal, because it allows me to apply my preferred axis of astigmatism. 

For a multifocal lens, it will give me an overlay to create my capsulotomy of desired size. For instance, a 5-mm capsulotomy will center over the visual axis. 

Also, once referenced, as the eye or scope moves so do the digital alignment markings. This can be invaluable as patients often have a hard time maintaining gaze, making it difficult to align capsulotomy and Purkinje reflexes.

Finally, at the end of the case, when I am putting the multifocal lens in the eye, there is a plus sign in the overlay that will tell me where the center of the visual axis is located, and it amazes me that this is not always exactly the center of the pupil.

 

We have found that in patients with higher chord mu values, the digital visual axis alignment is often not aligned with the center of the pupil.

There is no doubt that multifocal lenses have an inherent higher risk of causing dysphotopsia due to the multifocal nature of the design in the lens.

Physicians on quest to end dysphotopsias in premium IOLs



Glares, halos, and other dysphotopsias can be exacerbated if the patient is not looking through the center optic, especially the distant dominant optic. If the lens is not quite in the center of the visual axis and is positional slightly temporal to the visual axis, the patient might be looking through an edge of one of the rings, thus causing more postoperative symptoms. 

To minimize this adverse event, I want the center of the multifocal

 to be aligned with the center of the visual axis. The fovea, the center of the eye, should be looking right through the center of the multifocal 

. This can ensure that the quality of vision is not being compromised by the patient not looking through the center of the optic.


By using up-to-date formulas and advanced diagnostic tools, we can achieve a high probability of achieving our refractive target. Though we feel confident in achieving our targets, I can never guarantee a specific result to a patient. I always share with patients that there are risks and benefits to any procedure. 

There is always a need, potentially, for enhancement or the possibility for something to go wrong. But when I have confidence in the technology, it is conveyed naturally. 

I am not selling something; I am simply educating. And when I educate with confidence, it is easier for patients to consider the options. 




Paul Singh, MD, has no financial disclosures related to this content.

1. Zeng M, Liu Y, Liu X, et al. Aberration and contrast sensitivity comparison of aspherical and monofocal and multifocal intraocular lens eyes. 

. 2007;35(4):355-360. doi:10.1111/j.1442-9071.2007.01452.x

2. Karhanová M, Pluháček F, Mlčák P, Vláčil O, Šín M, Marešová K. The importance of angle kappa evaluation for implantation of diffractive multifocal intra-ocular lenses using pseudophakic eye model. 

 2015;93(2):e123-e128. doi:10.1111/aos.12521.

3. Tchah H, Nam K, Yoo A. Predictive factors for photic phenomena after refractive, rotationally asymmetric, multifocal intraocular lens implantation.

 2017; 10(2):241-245. doi:10.18240/ijo.2017.02.10

Articles

Alternative method ensures lens is set properly during cataract surgery


For IOL placement, location is key

Achieving the best surgical outcomes means putting as much effort into choosing a consistent and predictable postoperative steroid as surgeons do into every other aspect of eye surgery. 

We do so much to standardize surgery and minimize variability. To produce reliably positive outcomes, we focus first on the preoperative assessment and biometry, and then on using surgical tools and techniques that help us achieve micron-level precision. We optimize the 

 before surgery and refine our minimally invasive surgical techniques to improve postoperative recovery.

After surgery, we need to apply the same control-focused mindset in prescribing a postoperative steroid. There is enough variability in generic steroids to potentially affect healing and IOP, challenge compliance, and even erode patient satisfaction in the month following

. We cannot let that happen to our patients, and we should not diminish all of the careful work we have done up to that point. 

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	To me, it is certainly not worth taking a chance with a generic steroid after surgery. Older generic drug formulations only needed to match the active ingredient of an original innovator or branded drug, not demonstrate equivalence. This included corticosteroids such as prednisolone acetate.

Today, generic drops still may not be 100% bioequivalent to their branded counterparts. Manufacturers are only required to prove 80% bioequivalence, matching only in the active molecule while free to differ significantly in where they outsource the vehicle, inactive ingredients and bottle make and construction. 

When good manufacturing processes are followed, the differences between branded and generic medications are minimal in ophthalmic solutions, where all of the active and inactive ingredients are dissolved. However, the common generic ophthalmic corticosteroids used today are formulated as suspensions, not solutions or emulsions. 

Branded drugs rely on advanced vehicles that improve a drug’s therapeutic properties. It is almost impossible to accurately duplicate these important vehicles because they rely heavily on certain milling and other manufacturing processes that affect the particle size, coating, mixing, and other vehicle characteristics.

A different vehicle and variation in the manufacturing process can cause several problems. The active molecule can settle in the new vehicle, so patients do not get the desired effect unless they shake the bottle, and patients have poor compliance with shaking the bottle postoperatively.
	
	

The dropless future: SLT as a first-line treatment for glaucoma


	
	In addition, differing pH levels can affect absorption. Buffering agents can be inadequate. The ocular surface problems and other side effects of benzalkonium chloride (BAK) preservative can be greater because some generics may use higher concentrations of BAK than the branded alternative.

In short, a drop’s efficacy, safety and tolerance are affected by the vehicle and other inactive ingredients that make up most of the bottle. This relationship can be used to our advantage, such as when brimonidine tartrate 0.1% (Alphagan P, Allergan) was developed by changing the inactive ingredients in the brimonidine tartrate 0.2% drop. 

The preservative was changed, thereby increasing the pH, giving us half the concentration of active medication with the same efficacy and fewer side effects.
	
	In addition, the concentration of bromfenac (Prolensa, Bausch +Lomb) was changed from 0.09% to 0.07% while maintaining efficacy by changing the pH of the vehicle. With generics, however, we do not consistently know how and from whom the manufacturer sources the inactive ingredients. There is no oversight of the bottle’s contents, so it is no surprise that efficacy and tolerability can vary. 

It should be noted that in many cases, there is little or no savings in purchasing a generic steroid drop. Many generics are very close in price to branded counterparts, and manufacturers of new branded drugs typically offer coupons. Even if there is some small savings, to me it is not worth it to add potential unpredictability to the surgical recovery process. 

We have tried to educate our patients to provide them with enough understanding of the differences between a branded and generic medication so they can make a better decision on their own if it is worth it for them to pay the potentially higher cost. Essentially, we place value on everything we purchase, so providing patients with this knowledge is crucial for them to make an informed decision. 
	
	

Branded versus generics: You make the call in dry eye 


	In addition to sticking to the predictability of branded drops, it is important for me to factor IOP control into the selection of a steroid. I routinely perform not only cataract surgery, but also almost every type of glaucoma procedure. 

I am concerned about pressure spikes in patients with glaucoma who undergo any kind of eye surgery, but I am most worried when they have surgery that does not address glaucoma. For example, in cataract surgery without a concomitant 

minimally invasive glaucoma surgery (MIGS)

, patients can get significant pressure spikes postoperatively. 

Many years ago, a study by Armaly showed a significant rise in pressure in 95% of primary open-angle glaucoma (POAG) patients treated with steroids.

 About 50% of POAG patients had an IOP above 40 mm Hg at two weeks. I have seen pressure rise within the first week in 

patients on a certain steroids, such as difluprednate (Durezol, Novartis), an emulsion.
	
	

Genetic variants linked with onset, progression of POAG


	
	We also know that almost all low-tension glaucoma patients are steroid responders. We always need to be aware of that risk.

Loteprednol is a molecule used to minimize that risk. I have long used loteprednol for 

with or without MIGS, trabeculectomy, canaloplasty, XEN (Allergan), Hydrus (Ivantis), and other MIGS procedures because I am very comfortable with both its efficacy and its comparatively low risk for pressure spikes. There used to be a misconception that because loteprednol did not cause the same rate of pressure spikes as prednisolone, it was not as powerful as other steroids, but now we understand that this is not the case. It delivers the necessary efficacy with lower risk to IOP.


	After years of using loteprednol postoperatively, I was very comfortable trying a new formulation comprised of loteprednol nanoparticles with a mucus-penetrating surface coating (Inveltys, Kala Pharmaceuticals), an ophthalmic suspension, which offers better penetration of the mucin layer and cornea as well as less elimination with tears.
	
	The vehicle keeps the nanoparticles with their proprietary coating equally distributed in solution, playing an important role in ensuring patients get the amount of medication they need.

The drop’s improved bioavailability of active medication in the anterior chamber makes it possible to get the same results with BID dosing I had with other suspension steroid formulations with QID dosing. In my opinion, we cannot underestimate the value of a BID drug versus a QID drug for improving compliance.
	
	

Considering BID ocular steroid post-cataract surgery 


	
	As a glaucoma specialist, I always deal with eye drop compliance problems, from physical limitations to forgetfulness to ocular surface discomfort. Any time I can decrease the number of medications on the eye, I take that opportunity. BID dosing is simpler, so there’s less room for patient confusion and compliance errors. 

Patients appreciate the convenience as well. We asked our patients, three months after

 when everything is healed, if any factor negatively affect their happiness with this experience. Their top problem was taking so many drops every day after surgery. Now they can use fewer drops. And there’s no tapering-just BID dosing until the bottle runs out. 

This makes the regimen is less confusing throughout recovery, and it is an especially welcome change when patients have the fellow eye done and can follow the same schedule for both eyes.
	
	In fact, simplifying the regimen to BID dosing has actually saved us 2 to 3 minutes of staff time normally spent verifying the tapering medications for the first eye and educating patients about the dosing schedule, which, in turn, improved office flow in general. 
	
	


	Last year, I saw a patient who had used generic prednisolone acetate after cataract surgery. She was happy at one week with 20/25 vision, but unhappy at two weeks with 20/60 vision. Prednisolone was reducing inflammation, but the generic formulation was aggravating the ocular surface and affecting her vision. (See Figure 1)
	
	Inveltys had just been released, so I prescribed it after doing her second eye two weeks later. She was 20/20 and happy at one week, and the ocular surface looked much better compared to the prednisolone acetate eye. 

It is not a direct comparison-these drops have two different active molecules-but the case illustrates just how destructive the generic vehicle can prove to be.

The detrimental effects of some generic formulations are not always so pronounced and may not always be clinically significant, but the possibility is always there.
	
	By carefully choosing a branded steroid, we get an approach that works clinically, improves compliance (which can make our patients happier), and also saves us time-all while delivering the reliable control over postoperative recovery that we all want. And when significant pharmacological advances come along to help our patients, we are not limited to older generic options. 
	
	

Dr. Singh is president of the Eye Centers of Racine and Kenosha, Racine, WI. 

Roberts CW, Nelson PL. Comparative analysis of prednisolone acetate suspensions. 

Walsman AM, Antes A, Rescigno RJ, Lutz D, Lama PJ. What is in a drop? Brand versus generic prednisolone acetate formulations: A quantitative analysis.

 Investigative Ophthalmology & Visual Science

. ARVO Annual Meeting Abstract. 2007 May;48(13):5825.

Armaly MF. Effect of corticosteroids on intraocular pressure and fluid dynamics. I. The effect of dexamethasone in the normal eye. II. The effect of dexamethasone in the glaucomatous eye. 

Pleyer U, Ursell PG, Rama P. Intraocular pressure effects of common topical steroids for post-cataract inflammation: Are they all the same?

Fong R, Leitritz M, Siou-Mermet R, Erb T. Loteprednol etabonate gel 0.5% for postoperative pain and inflammation after cataract surgery: Results of a multicenter trial.

Rajpal RK, Roel L, Siou-Mermet R, Erb T. Efficacy and safety of loteprednol etabonate 0.5% gel in the treatment of ocular inflammation and pain after cataract surgery. 

Predictable, branded steroids offer control over surgery 

Supplemental treatments, such as Ginkgo biloba and a host of other antioxidants, can help address the systemic sources of ocular nerve damage and help to improve blood flow to the eye.

Glaucoma, as one of the leading causes of blindness and currently affecting up to four million Americans, is a general name given to a group of optic neuropathies characterized by the degeneration of the optic nerve, and age, race, family history, and elevated IOP are widely known risk factors for the disease.

While high IOP is currently the only modifiable risk factor, 15% to 30% of persons with ocular hypertension never develop glaucoma pathology, and conversely, patients with acceptable IOP still sustain ocular nerve damage.

Despite significant strides in diagnostic technology and advanced clinical treatment modalities, there are still many questions as to the causal root of glaucoma. Prevalent glaucoma management protocols aim to reduce and control IOP levels but may neglect to address the systemic sources of ocular nerve damage.

Compromised vascular function, both systemic and locally, has long been linked to open-angle glaucoma (OAG). Low systemic blood pressure has been correlated to low tension glaucoma and increased visual field loss in OAG. Diseases indicative of defective vasoregulation, such as Raynaud’s phenomenon and migraines, have also been correlated to normal tension glaucoma.

A 2009 consensus paper and subsequent corroborative studies point to decreased cerebrospinal fluid pressure (CSFP) as a contributing factor of ocular nerve damage.

The Leuven Eye Study sought to narrow down what vascular data can be used for disease stratification and found that glaucoma patients had higher ocular perfusion pressure, lower retrobulbar velocities, higher retinal venous saturation and higher choroidal thickness asymmetry as compared to healthy eyes.

The Leuven Eye Study built upon previous evidence suggesting that impaired vascular autoregulation renders the optic nerve head susceptible to ischemic damage, which likely contributes to further impairment in autoregulation and changes to the optic nerve head.

The secondary changes to ischemic damage may then begin a cascade of toxic by-products and free radicals that further deteriorate the health of the eye.

While it has not yet been established that maintaining or enhancing ocular blood flow will prevent glaucoma or slow its progression, there is certainly much scientific data pointing to a positive theoretical relationship between adequate nutrient delivery and the health of retinal ganglion cells.

Since improving ocular blood flow is not a treatment for nerve damage, but rather a potentially preventative therapy, it is a prime space to consider nutritional dietary supplementation. Limited studies have investigated the ability of the antioxidant Ginkgo biloba to improve ocular blood flow. Other antioxidants, anthocyanins and anthocyanidins, have been shown to increase optic nerve head and retinal blood flow, as well as slow visual field deterioration and influence ophthalmic function in other ways.

A recent study examined the effects of a nutritional dietary supplement (Optic Nerve Formula, ScienceBased Health) on retinal and retrobulbar blood flow in patients with open angle glaucoma (OAG). The study, a double blind, randomized, placebo control crossover study of nutritional supplements, was the most rigorous study to date. Previous studies of nutritional supplements were observational pilot studies focused on normal-tension glaucoma and healthy subjects.

Study participants included 45 people with confirmed OAG who were given active or placebo treatment for one month followed by washout and switched treatments.

Nutritional supplementation produced statistically significant improvements over placebo in: peak systolic and/or end diastolic blood flow velocities in all retrobulbar blood vessels, vascular resistance in the central retinal and nasal short posterior ciliary arteries, superior and inferior temporal retinal capillary mean blood flow, and the ratio of active to nonactive retina capillaries.

The study concluded that one-month oral administration of antioxidants produced increases in biomarkers of ocular blood flow within retinal and retrobulbar vascular beds and suggests that daily supplementation with certain antioxidants over a period of at least one month may improve retinal capillary perfusion in patients with OAG.

Integrating nutrition into clinical practice

Nutrition is increasingly gaining recognition among physicians and patients for its role in our overall health, and there is precedence for the efficacy of vitamins in ophthalmology.

While nutraceutical therapy is not an approved therapy, but an adjunct therapy, I frequently introduce it to my patients.

I explain that glaucoma is a disease that is primarily nerve damage due to one or several different causes. One of those causes could be pressure that is too high for their eyes, and that I will do what I can to bring that pressure down.

However, decreasing the pressure may not be enough to protect the nerve, but we can provide better nutrients to potentially help the blood supply and reduce inflammation very safely with oral antioxidant supplements.

I strongly recommend my patients use a product with scientifically backed ingredients, like bilberry extract, which are safe to take in conjunction with other medications and in individuals with fluctuating blood pressures. Patients leave my office with the understanding that there is virtually no downside, and that supplementation is an additional approach we can take to protect the nerve.

I am not comfortable sending patients out to purchase a generic supplement and only recommend well-studied supplements, such as the product used in the study, that adhere to strict quality control and consistency of makeup.

While much more study and clinical experience remains to be done on nutraceuticals, we have the ability to potentially improve vascular regulation and blood flow to the eye and reduce oxidative stress in a completely harmless and cost-effective manner.

If we have patients with blood flow related risk factors, I do feel it is important to educate them that there is an objectively studied supplement from which they may benefit.

As physicians, we can feel good knowing we have offered another pathway to protect precious nerve cells.

Dr. Singh is a glaucoma specialist practicing at The Eye Centers of Racine and Kenosha in Wisconsin. He did not indicate any proprietary interest relevant to the subject matter.

Author | Inder Paul Singh, MD

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