A Response to: Letter to the Editor Regarding “VIVEX—A Formula for Calculating Individual Vitreous Volume: A New Approach Towards Tailored Patient Dosing Regime in Intravitreal Therapy”

Dear Editor,

With great interest we have read the Letter to the Editor from Erduran et al. regarding our experimental study to calculate the individual vitreous volume more precisely [1]. We very much appreciate the interest in our study and the positive response expressed by the authors in their letter [2]. The authors agree that a more precise calculation of the individual vitreous volume and thus customized intravitreal drug application and customized approach in intravitreal surgeries (oil or gas tamponade) could have advantages over a “one-size-fits-all” strategy. However, the authors point out that the lens status (phakic or pseudophakic) could play an important role in the calculation of the vitreous body volume. They refer to a study by Santana et al. and quote as follows: "Santana et al. proposed an equation to estimate the vitreous cavity volume (VCV) in pseudophakic patients based on the axial length (AL) of the eye and estimated that the VCV should be 0.6–0.7 ml less than in pseudophakic patients” [3]. Therefore, Erduran et al. ask in their Letter to the Editor whether the status of the lens has an influence on the calculation of the vitreous body volume in our VIVEX calculation formula.

First, we would like to thank Erduran et al. for the positive feedback and their valuable comment. We are familiar with this study of Santana et al., as it was included in our manuscript’s reference list. We would also like to point out the “Limitations of the study”, which we stated at the end of our manuscript. We discussed the significance of lens status when starting to develop the calculation formula [4]. An interaction of AL, corneal power (K), and power/shape of the anatomic crystalline lens accounts for the ocular refractive state and this can change over time. It is clear that there are various anatomical factors that may influence the exact volume of the vitreous, including staphyloma in high myopia. It is well known that the steady growth of the crystalline lens with age and the development of cataracts can also lead to anatomical changes. The aim of our experimental study was to create awareness of the problem of a one-size-fits-all drug installation in the vitreous and to design a simple formula for approximation of the vitreous volume.

However, even if we expect some gain of vitreous volume after cataract surgery with implantation of an intraocular lens (IOL), we would like to exemplarily present a clinical case which shows that the lens status (phakic or pseudophakic) may be of minor relevance.

Figure 1 shows magnetic resonance images (MRI) of a patient with progressed cataracts in 2021 and the same patient after cataract surgery and implantation of an acrylic, one-piece intraocular lens in 2023. All of the MRI images were made with the same device (Siemens MAGNETOM Skyra 3T) and under identical conditions. The Siemens Skyra software was used to measure distances. The thickness of the cataractous lens and the intraocular lens was measured. Moreover, the vitreous depth (distance between the posterior lens/IOL surface and the retina, DPLR) in the phakic and pseudophakic eyes was measured. It could be proven that artificial lenses are thinner than natural lenses, thus increasing the DPLR after surgery (difference between crystalline lens and IOL thickness around 3 mm) This was expected and already described together with a deepening of the anterior chamber after cataract removal [5]. However, the DPLR in the phakic eye was 20.02 mm (right eye) and 19.90 mm (left eye) compared to 21.25 mm (right eye) and 21.20 mm (left eye) in the pseudophakic eye. This results in a difference in length of only 1.23 mm (right eye) and 1.30 mm (left eye).

We would like to discuss this fact as follows: The minor difference in the distance between the lens and the retina (DPLR) is due to the fact that the center of mass of the crystalline lens is located more anteriorly than the center of mass of the IOL. As intended by the IOL manufacturers, modern IOLs are designed in a way that the posterior optics surface is in contact with the posterior capsule to maintain the barrier function of the sharp optic edge for prevention of posterior capsular opacification.

There are numerous IOLs on the market (C-loop versus plate-haptics) with very different optics and haptics designs and materials (e.g., with additional clues such as step-vaulted and angulated haptics or wide optic–haptic junctions trying to prevent posterior capsule opacification; PCO). Experimental studies have shown differences in the behavior of IOLs depending on the compression and diameter of the capsule [6]. In short, modern one-piece acrylic lenses are designed to press firmly against the posterior capsule for best stability and long-term results. It is clear that the position of the IOL in the pseudophakic eye influences the refractive outcome of cataract surgery, and the different methods used for predicting the so-called “effective lens position” (ELP) are the main milestones in the evolution of biometric IOL power calculation formulas [7‐9]. All of these variabilities make it difficult to properly give a good estimate for the anatomical position of the IOL in the capsular bag that is valid for all eyes and all lens designs. We were able to show that there is a major increase in anterior chamber depth but a minor increase of the vitreous depth (DPLR) after cataract surgery with implantation of an IOL. This can be well documented with modern optical biometers or MRI (Fig. 2). As a cross-check, a volume calculation of the vitreous cavity using the software of the MRI device (similar to that used in radiology for various oncological cases) also showed no significant differences depending on the lens status (phakic versus pseudophakic).

We believe that changes/increase in the vitreous volume after cataract surgery has a minor effect since modern IOLs tend to attach to the posterior capsule. In addition, the back surface of the lens/IOL only makes up a small part of the three-dimensional vitreous cavity and does not change anything peripherally. This can be clearly shown using our eye model (Fig. 3). Therefore, we expect that slight changes in the DPLR are of minor clinical relevance when calculating the individual vitreous volume.

In summary, it is expected that with cataract surgery the vitreous volume will slightly increase. As the amount of volume gain is small and may vary with the design of the lens haptics and optics as well as the material properties, we recommend our VIVEX formula for a prediction of vitreous volume for phakic and pseudophakic eyes. Another intention of the laboratory experiment was to show that a general assumption of a “standard volume” of 4–5 ml is not appropriate. The formula is to be understood as a kind of starting point to carry out further studies quickly and easily to analyze the advantages and disadvantages of such a customized approach in intravitreal therapy and posterior segment surgery. Figure 2 shows the currently valid calculation. The formula should provide a better approximation and it seems that a maximum of one decimal place is sufficient to obtain an assessment between large, small, and standard volumes. It is conceivable that, similar to the evolution of IOL calculation formulas (first generation to date), advancements in technology (e.g., optical coherence tomography) will make the calculation even more accurate in the future [10].