Year : 2003 | Volume
: 51 | Issue : 3 | Page : 237--242
Intraocular Irrigating Solutions. A Clinical Study of BSS Plus® and Dextrose Bicarbonate Fortified BSS® as an Infusate during Pars Plana Vitrectomy.
Michael A Samuel, Uday R Desai, I Strassman, M Abusamak
Henry Ford Health System, Detroit, MI 48202, USA
Michael A Samuel
Henry Ford Health System, Detroit, MI 48202
Purpose: To compare the effect of Balanced Salt Solution Plus (BSS Plus, Alcon Laboratories, Fort Worth, Texas, USA) and fortified regular BSS on the cornea and lens, when used for continuous irrigation in pars plana vitrectomy (PPV) surgery. Methods: Prospective, investigator masked, randomised study. Forty patients were randomly assigned to undergo PPV using BSS Plus (n=20) or fortified BSS (n=20) [regular BSS, fortified with 10.5 cc. of dextrose in water (D5W) and 13.1cc. of 8.4% sodium bicarbonate]. Intraoperative features of the corneal epithelium, postoperative changes in the corneal endothelial cell denstiy (ECD) at 3 months, and clarity of the lens during surgery and postoperatively were evaluated. Results: Intraoperative epithelial changes were similar in both groups with 7 (35%) of the cases having the epithelium removed in the BSS Plus group and 8 (40%) in the BSS fortified group (P=0.23). The mean differences in ECD (3 months versus preoperative) in the operated eyes when adjusted for changes in the control eye showed no difference with the type of BSS (P=0.98). Intraoperative lens changes were more significant (P=0.018) in the BSS fortified group. Postoperative lens status at 3 months was similar for both groups. Though there was a trend towards worse postoperative nuclear sclerosis change in the BSS fortified group, it was not significant (P=0.160). Conclusion: Standard BSS fortified with dextrose and bicarbonate is an efficacious infusion fluid during pars plana vitrectomy. Both solutions showed comparable effects on postoperative corneal endothelial cell density and corneal epithelial changes intraoperatively. BSS fortified has more lenticular changes intraoperatively than BSS Plus although no lens had to be removed in either group. The study implications are important since BSS fortified is significantly less expensive than BSS Plus.
|How to cite this article:|
Samuel MA, Desai UR, Strassman I, Abusamak M. Intraocular Irrigating Solutions. A Clinical Study of BSS Plus® and Dextrose Bicarbonate Fortified BSS® as an Infusate during Pars Plana Vitrectomy. Indian J Ophthalmol 2003;51:237-242
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Samuel MA, Desai UR, Strassman I, Abusamak M. Intraocular Irrigating Solutions. A Clinical Study of BSS Plus® and Dextrose Bicarbonate Fortified BSS® as an Infusate during Pars Plana Vitrectomy. Indian J Ophthalmol [serial online] 2003 [cited 2020 Apr 5 ];51:237-242
Available from: http://www.ijo.in/text.asp?2003/51/3/237/14676
Infusion fluids continuously bathe structures in the eye including the cornea, lens and retina. The structures that seem most sensitive to changes are the crystalline lens and the corneal endothelium. It is imperative for the immediate and long-term success of intraocular surgery to maintain the clarity of these structures.
The ideal infusion fluid for pars plana vitrectomy should be easy to make, stable, inexpensive, and similar to aqueous fluid in its composition. None of the infusion fluids evaluated so far exactly mimics the aqueous humor. The complex composition of the aqueous humor makes exact duplication of its contents difficult. Solutions that have been less than ideal include 0.9% normal saline, Ringer's solution, balanced salt solution, plasma-lyte 148 and TC Medium 199.,,,, These solutions all lack some of the components present in aqueous humor.
The question arises as to which components are most necessary for a reasonably efficacious infusion fluid. McCarey and Edelhauser stated that the following were required: calcium is fundamental to the maintenance of the corneal endothelial junctional complexes and normal physiological functioning of the lens; bicarbonate is the normal physiologic buffer and helps maintain the function of the corneal endothelial cells; glucose is an energy source for both the lens and cornea; and reduced glutathione and adenosine support the corneal endothelial pump mechanism.
Based on this understanding, they developed a solution called Glutathione - Bicarbonate - Ringer's Solution (GBR). The GBR solution was shown to be superior to other solutions in corneal perfusion studies., Christiansen also showed some superior results using GBR in lens incubation studies when compared to less ideal solutions. These results led to the more widespread acceptance of this infusion fluid for pars plana vitrectomy. GBR was later modifed to achieve better stability of its component parts, by replacing adenosine and reduced glutathione with oxidized glutathione. This solution we now know as Balanced Salt Solution Plus.
Balanced Salt Solution Plus (BSS Plus) continues to be widely used during vitrectomy surgery. In the late 1970s McEnerney and Peyman found that one of the crucial elements of BSS Plus, the glutathione, could be omitted from the infusion fluid as long as glucose and bicarbonate were present. This was supported by a recent study by Puckett which showed no significant difference in the corneal endothelial cell characteristics after extracapsular cataract extraction in patients who had an infusion of BSS Plus or a lactated Ringer's solution fortified with dextrose and bicarbonate.
Since the majority of studies compared use of BSS Plus with inferior solutions in pars plana vitrectomy, it is not clear whether the expense of BSS Plus is justified compared to other less expensive alternatives. We chose to compare BSS Plus with regular BSS fortified with dextrose and bicarbonate as described by McEnerney and Peyman. Our goal was to assess and compare the intraoperative and postoperative effects on the cornea and crystalline lens by these infusion fluids during pars plana vitrectomy.
Materials and Methods
This was a prospective, masked and randomised study that evaluated the effect of two different vitrectomy infusion fluids on the cornea and the crystalline lens. A random number generator assigned 40 patients to one of the two groups. Twenty patients were assigned to undergo pars plana vitrectomy (PPV) using Balanced Salt Solution Plus (BSS Plus). A second group of 20 patients was assigned to undergo PPV using regular Balanced Salt Solution fortified with 10.5cc dextrose in water (D5W) and 13.1cc 8.4% sodium bicarbonate (BSS fortified). A new 250cc bag of D5W was used each day. A sterile syringe was used to extract 10.5cc and inject it into the new BSS bottle. A new sterile 50cc ampoule of 8.4% sodium bicarbonate was used each day. A sterile syringe was used to extract 13.1cc and inject it into the BSS bottle. The surgeon was masked to the composition of the infusion fluid. Outcome measures included intraoperative and postoperative changes in the cornea and the crystalline lens. Intraoperative evaluation of the cornea included an assessment of the corneal epithelium during PPV. We developed our own scoring system to quantify changes to the corneal epithelium. A score of 1-3 was assigned, corresponding to 1 - no change in the epithelium, 2 - mild change in the epithelium, and 3 - epithelium removed. Intraoperative evaluation of the crystalline lens involved a subjective assessment by the surgeon of the clarity of the lens. Again, we developed our own scoring system to assess these changes. A score of 1-4 was assigned, which indicated: 1 - no change, 2 - clinically insignificant change, 3 - clinically significant change, and 4 - lens removed.
Postoperatively, changes in the cornea were assessed by evaluating corneal endothelial cell density by specular microscopy at 3 months and comparing them to preoperative measurements. Central corneal the endothelial cell density (ECD) was calculated from the endothelial photographs taken by a contact-type Konan Clinical Specular Microscope (Japan) with a 40x dipping cone objective. The ECD was also done on the opposite eye preoperatively and at 3 months postoperatively. The investigator who measured the endothelial cell density was masked to the composition of the infusion fluid. Postoperative changes in the crystalline lens were assessed by assigning a lens score of 0 - 3 for nuclear sclerosis, cortical spoking, and posterior subcapsular changes. Clinical standards set by the age-related eye disease study (AREDS) were used to assess the correct lens score for each of the three components.12 The surgeon made the lens measurements preoperatively and and at 3 months postoperatively. To assess whether time of surgery was associated with changes in the lens or cornea we also measured the intraocular surgical time. This was to estimate the length of time the eye structures were exposed to the infusion fluid. The duration was measured from the time the infusion cannula was opened until the infusion cannula was removed from the eye.
The study included patients who had pars plana vitrectomy performed by one vitreoretinal surgeon. Consecutive patients who were scheduled for pars plana vitrectomy were evaluated for possible inclusion in the study. Inclusion criteria included the ability to provide informed consent and to come for follow-up exams for a minimum of three months. Phakic and pseudophakic patients were included in the study. Diabetic patients were also included. Exclusion criteria included previous corneal pathology, lens opacification severe enough to prevent good visualisation, aphakia, AIDS patients with CMV retinitis, patients who required the placement of silicone oil, and patients in whom the intraoperative lens had been touched by intraocular instruments.
The mean age of 40 patients was 61.9± SD 12.7 (range, 34-84). The gender, mean age, and lens status of the two groups is illustrated in [Table 1]. The mean age of patients in the BSS Plus group is higher than the BSS fortified group. The proportion of phakic to pseudophakic patients was similar in both groups. Indications for surgery are listed in [Table 2]. The most common diagnosis in both groups was non-clearing vitreous haemorrhage related to diabetic retinopathy. Tractional retinal detachments were seen more often in the BSS fortified group. Other less common indications for surgery include rhegmatogenous retinal detachment, non-diabetic vitreous haemorrhage, macular hole, epiretinal membrane, and cystoid macular oedema. The mean duration of surgery was 44.05 minutes for the BSS Plus group and 39.05 minutes for the BSS fortified group (P = 0.64).
Intraoperative corneal epithelial changes were similar in both the BSS Plus and the BSS fortified groups The corneal epithelium was removed in 7 patients (35%) in the BSS plus group and in 8 patients (40%) in the BSS fortified group ( P = 0.23) [Table 3]. In both groups the duration of surgery was related to an increase in epithelial breakdown ( P = 0.006).
To determine the longterm effect of surgery on the corneal endothelium, the endothelial cell density measurements were done. All patients had a mean ECD of 2192 ± 516 preoperatively. The mean ECD was 2132 ± 515 for all patients postoperatively. The ECD percentage decrease for all patients was 2.4±9.4. There was no significant difference in percent decrease in ECD at three months postoperatively between BSS Plus (3.8%) and BSS fortified (1.0%), [Table 4]. The difference between the endothelial cell density at 3 months postoperatively and the preoperative measurements was calculated for both the operated and fellow eye. The mean difference in the BSS Plus group was 70.0 cells per square millimeter, compared to 50.0 cells per square millimeter for the BSS fortified group (P = 0.84). The mean differences in endothelial cell counts (3 months - preoperative) were - 70.9 cells/sq mm in phakic patients and 22.2 cells/sq mm in pseudophakic patients (P = 0.69). The mean difference in endothelial cell counts (3 months - preoperative) in the operated eyes when adjusted for changes in the control eye showed no differences when evaluating the types of BSS (P = 0.98), lens status (P = 0.38), epithelium status (P = 0.48), age
(P = 0.99), or surgery time ( P = 0.38).
Excluding pseudophakic patients, intraoperative lens changes were more significant (P = 0.018) in the BSS fortified group. Five (31.25%) patients in the BSS fortified group had no change in their lens, 50% (n = 8) had clinically insignificant change, 18.75% (n = 3) had clinically significant change, and no one (n = 0) had their lens removed during surgery. This compared with 80% (n = 12) having no changes in their lens, 20% (n=3) having clinically insignificant change, 0% (n = 0) with clinically significant change, and none having their lens removed in the BSS Plus groups [Table 5]. There were no cases of intraoperative lens touch.
Postoperative lens changes at 3 months showed no significant worsening of the cortical, nuclear, or posterior subcapsular lens score in either the BSS Plus or the BSS fortified group. While the BSS fortified group did show a trend towards worsening of the nuclear score at 3 months compared to the BSS Plus group, it did not reach statistical significance (P = 0.160) [Table 6].
The success of pars plana vitrectomy depends to an extent on maintaining a clear surgical view during the procedure and during the postoperative period. Infusion fluids during PPV continually bathe the intraocular structures and are important in maintaining the clarity and function of these structures. BSS Plus has been shown to be superior to other infusion fluids (BSS, lactated Ringer's solution, normal saline) in its ability to maintain corneal endothelial function and corneal clarity. ,, The other, less-than-ideal fluids lacked the components necessary for optimal functioning of intraocular structures [Table 7]. These missing components might include an energy source, a physiologic buffer, physiologic ions, or an osmolality comparable to aqueous. For example BSS contains no energy source, making it hypotonic to aqueous humor and more alkaline in pH [Table 7], BSS also uses an acetate-citrate buffer as opposed to bicarbonate, which is the normal aqueous humor buffer. Similar to plain BSS, lactated Ringer's solution as well as normal saline clearly lack elements which make them less than physiologic.
In our study we fortified standard BSS with 13.1cc of 8.4% sodium bicarbonate and 10.5cc of dextrose (D5W) so it more closely resembled aqueous humor than did previously compared solutions. Our fortified BSS solution is comparable to BSS Plus in that both contain an energy source and a bicarbonate buffer. Both also have an osmolarity, pH, calcium, and magnesium ions that resemble the physiologic aqueous. The main difference between our two solutions was the lack of oxidized glutathione (GSSG) in the fortified BSS. The oxidized glutalthione is reported to protect the corneal endothelium.,,, As a result BSS Plus may be more beneficial for phacoemulsification cataract surgery, which is potentially more stressful to the endothelial cells.
Our study did not show a significant clinical advantage in using BSS Plus with its associated glutathione over standard BSS fortified with dextrose and bicarbonate as an infusion fluid in pars plana vitrectomy. The postoperative changes in the corneal endothelial cell counts were similar for the two groups. Intraoperative lens changes were statistically worse in the BSS fortified group with 18.75% (n = 3) developing a clinically significant lens change during surgery, although no lenses had to be removed. Postoperative lens changes were similar between the two groups although there was a trend towards worsening of the nuclear score in the BSS fortified group that was not statistically significant.
Lens changes are the most common complication of pars plana vitrectomy and worsening nuclear sclerosis cataract formation is well established. The pathogenesis of post-vitrectomy lens changes at present is unclear, although several mechanisms have been proposed. These include intraoperative light toxicity,  intraoperative oxidation of lens proteins,  and surgery induced changes of the lens' biochemical micro-environment. Longer duration of surgery had been suggested as a possible contributing factor  but recently Cheng et al, suggested that this may not be true. There was no significant difference in the intraoperative surgical time between the two groups in this study and hence the duration of surgery was not a factor responsible for the differences in lens changes. The fact that there was no significant difference between the groups with regard to worsening of postoperative cataract formation is encouraging. We should note that our follow-up for lens status evaluation was no longer than three months. Longer follow-up could have possibly shown changes, which may have benefited one group over the other.
In our study no lens had to be removed intra-operatively in either group. The fact that a majority of the patients in both groups were diabetic makes this finding even more critical. Matsuda et al, suggested that absence of the lens is contributing factor in corneal endothelial damage during vitrectomy. They believe that the lens provides an important mechanical barrier and reduces endothelial damage. The maintenance of lens clarity in both study groups may have been influenced by the presence of glucose in both BSS Plus and BSS fortified. The presence of glucose in the infusion fluid is known to reduce the incidence of intraoperative lens opacification in diabetic patients undergoing vitrectomy. It would seem obvious that the BSS fortified group would not have fared as well had glucose been omitted.
In this study we chose to measure corneal endothelial cell density as an indicator of endothelial function as opposed to corneal thickness in previous studies. The corneal thickness is not a sensitive or reliable indicator of endothelial dysfunction. An earlier study by Rosenfeld et al did not show any difference in corneal oedema and endothelial cell loss using either BSS or BSS Plus in pars plana vitrectomy. However, use of endothelial cell density is not without problems. This includes inaccuracies of the measurements themselves in addition to sampling errors. We also acknowledge that the newer endothelial cell morphology analysis techniques may be more sensitive and reliable in detecting subtle changes in endothelial cells. All the same, polygonality measurements could have the greatest remeasurement error. In our study we only looked at endothelial cell counts before surgery and at 3 months after surgery. We do not know if this time period was long enough to determine the effect of theses two solutions on the endothelium. The normal endothelium attrition is present throughout life, and perhaps these solutions may have a longterm effect on the corneal endothelium.
This study also evaluated the corneal epithelium during surgery as a proxy for intraoperative endothelial function. Infusion fluids during PPV directly perfuse the corneal endothelial cells which can certainly influence the epithelium. Other factors that could also affect the corneal epithelium are intraocular pressure during vitrectomy, over-hydration from the infusion fluids, length of surgery, and type of viewing lenses used during surgery. In our study, increased duration of surgery was associated with an increase in epithelial changes ( P = 0.006). All of our vitrectomies were also done using hand-held infusion lens. Since our study shows no difference in the corneal epithelial changes between the two groups, we can surmise that these two intraocular infuison fluids may not have any effect on the corneal endothelium.
Although BSS Plus appears to be an excellent intraocular infusion fluid during pars plana vitrectomy, its cost is significantly higher than standard BSS. At our institution we pay $45.00 for a 500ml bottle of BSS Plus and the standard BSS 500ml bottle costs $4.50. With the addition of our fortifying ingredients, D5W and NaHCO, the BSS Fortified costs approximately $6.00 for a 500ml bottle. This substantial savings equates to nearly $20,000 per surgeon in a year based on 500 vitrectomies a year. For our department, with four full time retinal surgeons on staff, the costs certainly may not be justified. The worldwide implications in cost savings are substantial especially in countries where resources may be limited or unavailable.
Among the limitations of this study are: first, this was a relatively small prospective study from one surgeon. While we feel the results are valid and meaningful, a larger study may be more persuasive. Second, the lens changes were assessed using the AREDS lens classification system. While two previous studies, have also used the AREDS lens classification system, this subjective measurement by the surgeon is likely to have an inherent weakness that could affect the outcomes. Finally, we did not measure any functional or anatomic outcomes such as success of surgery or visual acuity. As a result we cannot make any conclusions regarding the relative merits of these two solutions in maintaining or achieving retinal attachment. Similarly we cannot comment on the relative effects of these two solutions on ocular structures other than the lens and the cornea. While our clinical impression does not lead us to suspect any adverse effects to any other ocular structures for either of the two solutions, our methodology does not allow us to make such a conclusive statement.
In conclusion, standard BSS solution can be easily and cost-effectively fortified with dextrose and bicarbonate. BSS fortified with these components is an efficacious alternative to BSS Plus as an infusion fluid for pars plana vitrectomy.
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